Neurology

  • Article | | open

    FXR1P is a RNA binding protein involved in muscle development. Here, the authors show that mutations in FXR1 exon 15, which is alternatively spliced in muscle, cause multi-minicore myopathy in humans and in mouse models.

    • María Cristina Estañ
    • , Elisa Fernández-Núñez
    • , Maha S. Zaki
    • , María Isabel Esteban
    • , Sandra Donkervoort
    • , Cynthia Hawkins
    • , José A. Caparros-Martin
    • , Dimah Saade
    • , Ying Hu
    • , Véronique Bolduc
    • , Katherine Ru-Yui Chao
    • , Julián Nevado
    • , Ana Lamuedra
    • , Raquel Largo
    • , Gabriel Herrero-Beaumont
    • , Javier Regadera
    • , Concepción Hernandez-Chico
    • , Eduardo F. Tizzano
    • , Victor Martinez-Glez
    • , Jaime J. Carvajal
    • , Ruiting Zong
    • , David L. Nelson
    • , Ghada A. Otaify
    • , Samia Temtamy
    • , Mona Aglan
    • , Mahmoud Issa
    • , Carsten G. Bönnemann
    • , Pablo Lapunzina
    • , Grace Yoon
    •  & Victor L. Ruiz-Perez
  • Article | | open

    Valyl-tRNA synthetase (VARS) charges valyl-tRNA with the amino acid valine, required for translation. Here, the authors describe a progressive epileptic encephalopathy in individuals from five families carrying biallelic mutations in the VARS gene that leave the enzyme activity partially intact.

    • Jennifer Friedman
    • , Desiree E. Smith
    • , Mahmoud Y. Issa
    • , Valentina Stanley
    • , Rengang Wang
    • , Marisa I. Mendes
    • , Meredith S. Wright
    • , Kristen Wigby
    • , Amber Hildreth
    • , John R. Crawford
    • , Alanna E. Koehler
    • , Shimul Chowdhury
    • , Shareef Nahas
    • , Liting Zhai
    • , Zhiwen Xu
    • , Wing-Sze Lo
    • , Kiely N. James
    • , Damir Musaev
    • , Andrea Accogli
    • , Kether Guerrero
    • , Luan T. Tran
    • , Tarek E. I. Omar
    • , Tawfeg Ben-Omran
    • , David Dimmock
    • , Stephen F. Kingsmore
    • , Gajja S. Salomons
    • , Maha S. Zaki
    • , Geneviève Bernard
    •  & Joseph G. Gleeson
  • Article | | open

    tRNAs are linked with their cognate amino acid by aminoacyl tRNA synthetases (ARS). Here, the authors report a developmental encephalopathy associated with biallelic VARS variants (valyl-tRNA synthetase) that lead to loss of function, as determined by several in vitro assays and a vars knockout zebrafish model.

    • Aleksandra Siekierska
    • , Hannah Stamberger
    • , Tine Deconinck
    • , Stephanie N. Oprescu
    • , Michèle Partoens
    • , Yifan Zhang
    • , Jo Sourbron
    • , Elias Adriaenssens
    • , Patrick Mullen
    • , Patrick Wiencek
    • , Katia Hardies
    • , Jeong-Soo Lee
    • , Hoi-Khoanh Giong
    • , Felix Distelmaier
    • , Orly Elpeleg
    • , Katherine L. Helbig
    • , Joseph Hersh
    • , Sedat Isikay
    • , Elizabeth Jordan
    • , Ender Karaca
    • , Angela Kecskes
    • , James R. Lupski
    • , Reka Kovacs-Nagy
    • , Patrick May
    • , Vinodh Narayanan
    • , Manuela Pendziwiat
    • , Keri Ramsey
    • , Sampathkumar Rangasamy
    • , Deepali N. Shinde
    • , Ronen Spiegel
    • , Vincent Timmerman
    • , Sarah von Spiczak
    • , Ingo Helbig
    • , Chris Balak
    • , Newell Belnap
    • , Ana Claasen
    • , Amanda Courtright
    • , Matt de Both
    • , Matthew J. Huentelman
    • , Marcus Naymik
    • , Ryan Richholt
    • , Ashley L. Siniard
    • , Szabolcs Szelinger
    • , David W. Craig
    • , Isabelle Schrauwen
    • , Zaid Afawi
    • , Rudi Balling
    • , Stéphanie Baulac
    • , Nina Barišić
    • , Hande S. Caglayan
    • , Dana Craiu
    • , Rosa Guerrero-López
    • , Renzo Guerrini
    • , Helle Hjalgrim
    • , Johanna Jähn
    • , Karl Martin Klein
    • , Eric Leguern
    • , Johannes R. Lemke
    • , Holger Lerche
    • , Carla Marini
    • , Rikke S. Møller
    • , Hiltrud Muhle
    • , Felix Rosenow
    • , Jose Serratosa
    • , Arvid Suls
    • , Ulrich Stephani
    • , Katalin Štěrbová
    • , Pasquale Striano
    • , Federico Zara
    • , Sarah Weckhuysen
    • , Christopher Francklyn
    • , Anthony Antonellis
    • , Peter de Witte
    •  & Peter De Jonghe
  • Article | | open

    The brain primarily uses glucose to generate energy, but the relationship of neuronal activity to glucose utilization is not necessarily a simple linear one. Here, the authors introduce relative power (rPWR) and relative cost (rCST) as new metrics to quantify how brain activity relates to glucose consumption.

    • Ehsan Shokri-Kojori
    • , Dardo Tomasi
    • , Babak Alipanahi
    • , Corinde E. Wiers
    • , Gene-Jack Wang
    •  & Nora D. Volkow
  • Article | | open

    Lifestyle factors such as smoking and exercise contribute to the health of the brain during aging, but previous studies have focused on the effects of single lifestyle variables. Here, the authors examine the combined and individual effects of four lifestyle variables on brain structure and function.

    • Nora Bittner
    • , Christiane Jockwitz
    • , Thomas W. Mühleisen
    • , Felix Hoffstaedter
    • , Simon B. Eickhoff
    • , Susanne Moebus
    • , Ute J. Bayen
    • , Sven Cichon
    • , Karl Zilles
    • , Katrin Amunts
    •  & Svenja Caspers
  • Article | | open

    Nuclear envelopathies are a group of diseases caused by genetic mutations in essential nuclear envelope genes. Here, the authors report a nuclear envelopathy with a homozygous nonsense variant in TOR1AIP1 which leads to changes in the nuclear morphology including large nuclear-spanning channels in patients’ fibroblasts.

    • Boris Fichtman
    • , Fadia Zagairy
    • , Nitzan Biran
    • , Yiftah Barsheshet
    • , Elena Chervinsky
    • , Ziva Ben Neriah
    • , Avraham Shaag
    • , Michael Assa
    • , Orly Elpeleg
    • , Amnon Harel
    •  & Ronen Spiegel
  • Article | | open

    Midbrain dopamine (mDA) neurons are significantly associated with Parkinson’s disease and yet there is no systematic molecular classification of these heterogenous group of cells. Here authors use single cell RNA sequencing of isolated mouse neurons expressing the transcription factor Pitx3 (broad mDA neuronal marker) to identify and characterize seven neuron subgroups divided in two major branches of developing Pitx3-expressing neurons.

    • Katarína Tiklová
    • , Åsa K. Björklund
    • , Laura Lahti
    • , Alessandro Fiorenzano
    • , Sara Nolbrant
    • , Linda Gillberg
    • , Nikolaos Volakakis
    • , Chika Yokota
    • , Markus M. Hilscher
    • , Thomas Hauling
    • , Fredrik Holmström
    • , Eliza Joodmardi
    • , Mats Nilsson
    • , Malin Parmar
    •  & Thomas Perlmann
  • Article | | open

    Adeno-associated viral vectors (AAV) are being developed for gene therapy of skeletal muscle, but it is a challenge to achieve robust gene expression. Here, the authors identify muscle-specific cisregulatory elements that lead to a substantial increase in micro-dystrophin and follistatin expression, resulting in a safe and sustainable rescue of the dystrophic phenotype in mouse models.

    • S. Sarcar
    • , W. Tulalamba
    • , M. Y. Rincon
    • , J. Tipanee
    • , H. Q. Pham
    • , H. Evens
    • , D. Boon
    • , E. Samara-Kuko
    • , M. Keyaerts
    • , M. Loperfido
    • , E. Berardi
    • , S. Jarmin
    • , P. In’t Veld
    • , G. Dickson
    • , T. Lahoutte
    • , M. Sampaolesi
    • , P. De Bleser
    • , T. VandenDriessche
    •  & M. K. Chuah
  • Article | | open

    Blocking the PD-1 pathway was shown to be effective in amyloid beta mouse models, yet little is known about its therapeutic potential in models of tauopathy. The authors show here that blocking PD-L1, a PD-1 ligand, is similarly effective, and that both treatments reversed cognitive deficiencies, and modified disease pathology not only in an animal model of AD, but also in the DM-hTAU mouse tauopathy model, through a mechanism that involves monocyte-derived macrophages.

    • Neta Rosenzweig
    • , Raz Dvir-Szternfeld
    • , Afroditi Tsitsou-Kampeli
    • , Hadas Keren-Shaul
    • , Hila Ben-Yehuda
    • , Pierre Weill-Raynal
    • , Liora Cahalon
    • , Alex Kertser
    • , Kuti Baruch
    • , Ido Amit
    • , Assaf Weiner
    •  & Michal Schwartz
  • Article | | open

    Fibrinogen-like protein 2 (FGL2) mediates immune suppression in glioblastoma (GBM). Here, the authors show that FGL-2 expressed by GBM cancer cells acts by suppressing the differentiation of CD103+ DC cells required to activate the anti-tumor CD8+ T cell response via blocking GM-CSF signalling at NFKB, STAT1/5 and p38 level.

    • Jun Yan
    • , Qingnan Zhao
    • , Konrad Gabrusiewicz
    • , Ling-Yuan Kong
    • , Xueqing Xia
    • , Jian Wang
    • , Martina Ott
    • , Jingda Xu
    • , R. Eric Davis
    • , Longfei Huo
    • , Ganesh Rao
    • , Shao-Cong Sun
    • , Stephanie S. Watowich
    • , Amy B. Heimberger
    •  & Shulin Li
  • Article | | open

    The delivery of single therapeutic microRNAs in brain cancers is challenging. Here, the authors engineer three neuronal microRNAs (miR-124, 128 and 137) into a cluster that, targeting oncogenic chromatin repressors, increases survival of GBM-bearing mice when combined with chemotherapy.

    • Vivek Bhaskaran
    • , Michal O. Nowicki
    • , Mahmoud Idriss
    • , Miguel A. Jimenez
    • , Gianmarco Lugli
    • , Josie L. Hayes
    • , Ahmad Bakur Mahmoud
    • , Rachel E. Zane
    • , Carmela Passaro
    • , Keith L. Ligon
    • , Daphne Haas-Kogan
    • , Agnieszka Bronisz
    • , Jakub Godlewski
    • , Sean E. Lawler
    • , E. Antonio Chiocca
    •  & Pierpaolo Peruzzi
  • Article | | open

    Various types of genetic variation contribute to the etiology of intellectual disability (ID). Here, the authors study a cohort of ID patients enriched for mild ID from Finland, to investigate contributions of rare and common variants associated with ID of different levels of severity.

    • Mitja I. Kurki
    • , Elmo Saarentaus
    • , Olli Pietiläinen
    • , Padhraig Gormley
    • , Dennis Lal
    • , Sini Kerminen
    • , Minna Torniainen-Holm
    • , Eija Hämäläinen
    • , Elisa Rahikkala
    • , Riikka Keski-Filppula
    • , Merja Rauhala
    • , Satu Korpi-Heikkilä
    • , Jonna Komulainen–Ebrahim
    • , Heli Helander
    • , Päivi Vieira
    • , Minna Männikkö
    • , Markku Peltonen
    • , Aki S. Havulinna
    • , Veikko Salomaa
    • , Matti Pirinen
    • , Jaana Suvisaari
    • , Jukka S. Moilanen
    • , Jarmo Körkkö
    • , Outi Kuismin
    • , Mark J. Daly
    •  & Aarno Palotie
  • Article | | open

    Mutations in the mechanotransduction channel component TMC1/2 cause deafness. Here, the authors use a synthetic AAV to replace TMC1 and 2 in the inner ear and show restoration of cochlear and vestibular function, of neuronal reponses in the auditory cortex and of hearing and balance in mice.

    • Carl A. Nist-Lund
    • , Bifeng Pan
    • , Amy Patterson
    • , Yukako Asai
    • , Tianwen Chen
    • , Wu Zhou
    • , Hong Zhu
    • , Sandra Romero
    • , Jennifer Resnik
    • , Daniel B. Polley
    • , Gwenaelle S. Géléoc
    •  & Jeffrey R. Holt
  • Article | | open

    Medulloblastoma is one of the most prevalent malignant brain tumors in children and has very poor prognosis. In this study, the authors show, using a mouse model of medulloblastoma, that Gfi1 promotes tumor growth by recruiting Lsd1, that this interaction inhibits genes involved in neuronal differentiation, and that Lsd1 may be a therapeutic target in Gfi1-activated tumors.

    • Catherine Lee
    • , Vasilisa A. Rudneva
    • , Serap Erkek
    • , Marc Zapatka
    • , Lianne Q. Chau
    • , Silvia K. Tacheva-Grigorova
    • , Alexandra Garancher
    • , Jessica M. Rusert
    • , Ozlem Aksoy
    • , Robin Lea
    • , Helai P. Mohammad
    • , Jianxun Wang
    • , William A. Weiss
    • , H. Leighton Grimes
    • , Stefan M. Pfister
    • , Paul A. Northcott
    •  & Robert J. Wechsler-Reya
  • Article | | open

    There are currently no validated methods for the diagnosis of prion disease at the preclinical stage. Here the authors show that serial protein misfolding cyclic amplification and real-time quaking-induced conversion can be used to detect prions in the skin of prion-inoculated hamsters and humanized transgenic mice at early preclinical stages.

    • Zerui Wang
    • , Matteo Manca
    • , Aaron Foutz
    • , Manuel V. Camacho
    • , Gregory J. Raymond
    • , Brent Race
    • , Christina D. Orru
    • , Jue Yuan
    • , Pingping Shen
    • , Baiya Li
    • , Yue Lang
    • , Johnny Dang
    • , Alise Adornato
    • , Katie Williams
    • , Nicholas R. Maurer
    • , Pierluigi Gambetti
    • , Bin Xu
    • , Witold Surewicz
    • , Robert B. Petersen
    • , Xiaoping Dong
    • , Brian S. Appleby
    • , Byron Caughey
    • , Li Cui
    • , Qingzhong Kong
    •  & Wen-Quan Zou
  • Article | | open

    Meningitis is a severe form of invasive pneumococcal disease (IPD). To study the contribution of bacterial genomic variation, here Li et al. perform whole genome sequencing of pneumococcal isolates from IPD patients and identify an association for higher risk of meningitis with a pbp1bA641C variant

    • Yuan Li
    • , Benjamin J. Metcalf
    • , Sopio Chochua
    • , Zhongya Li
    • , Hollis Walker
    • , Theresa Tran
    • , Paulina A. Hawkins
    • , Ryan Gierke
    • , Tamara Pilishvili
    • , Lesley McGee
    •  & Bernard W. Beall
  • Article | | open

    The potential links between infections and neurodegenerative disorders are unclear. Here, Wu et al. present a mouse model of low-grade candidemia characterized by highly localized cerebritis, accumulation of amyloid precursor protein and beta peptides, and mild memory impairment that resolves with fungal clearance.

    • Yifan Wu
    • , Shuqi Du
    • , Jennifer L. Johnson
    • , Hui-Ying Tung
    • , Cameron T. Landers
    • , Yuwei Liu
    • , Brittany G. Seman
    • , Robert T. Wheeler
    • , Mauro Costa-Mattioli
    • , Farrah Kheradmand
    • , Hui Zheng
    •  & David B. Corry
  • Article | | open

    The frontal cortex is involved in cognitive control, e.g. cognitive flexibility and behavioral inhibition, but the roles of frontal subdivisions are unclear. Here, the authors used computational modelling of cognitive control task performance to map lesions responsible for impairments in specific cognitive operations.

    • Jan Gläscher
    • , Ralph Adolphs
    •  & Daniel Tranel
  • Article | | open

    Gene editing strategies are typically designed to correct mutant genes, but most neurodegenerative diseases are sporadic. Here the authors describe a strategy to selectively edit the C-terminus of APP and attenuate amyloid-β production, while upregulating neuroprotective α-cleavage.

    • Jichao Sun
    • , Jared Carlson-Stevermer
    • , Utpal Das
    • , Minjie Shen
    • , Marion Delenclos
    • , Amanda M. Snead
    • , So Yeon Koo
    • , Lina Wang
    • , Dianhua Qiao
    • , Jonathan Loi
    • , Andrew J. Petersen
    • , Michael Stockton
    • , Anita Bhattacharyya
    • , Mathew V. Jones
    • , Xinyu Zhao
    • , Pamela J. McLean
    • , Andrew A. Sproul
    • , Krishanu Saha
    •  & Subhojit Roy
  • Article | | open

    Schizophrenia (SCZ) risk is influenced by genetic and environmental factors. Here, the authors develop a statistical method for analyzing gene-by-environment effects in SCZ risk across Denmark with fine spatial resolution.

    • Chun Chieh Fan
    • , John J. McGrath
    • , Vivek Appadurai
    • , Alfonso Buil
    • , Michael J. Gandal
    • , Andrew J. Schork
    • , Preben Bo Mortensen
    • , Esben Agerbo
    • , Sandy A. Geschwind
    • , Daniel Geschwind
    • , Thomas Werge
    • , Wesley K. Thompson
    •  & Carsten Bøcker Pedersen
  • Article | | open

    Optogenetics is a promising alternative approach for restoration of neuromuscular function. Here the authors establish a closed-loop functional optogenetic stimulation for the control of limb joint angle in murine models, which demonstrates improved control and less fatigue than electrical stimulation systems.

    • Shriya S. Srinivasan
    • , Benjamin E. Maimon
    • , Maurizio Diaz
    • , Hyungeun Song
    •  & Hugh M. Herr
  • Article | | open

    Epilepsies are common brain disorders and are classified based on clinical phenotyping, imaging and genetics. Here, the authors perform genome-wide association studies for 3 broad and 7 subtypes of epilepsy and identify 16 loci - 11 novel - that are further annotated by eQTL and partitioned heritability analyses.

    • Bassel Abou-Khalil
    • , Pauls Auce
    • , Andreja Avbersek
    • , Melanie Bahlo
    • , David J. Balding
    • , Thomas Bast
    • , Larry Baum
    • , Albert J. Becker
    • , Felicitas Becker
    • , Bianca Berghuis
    • , Samuel F. Berkovic
    • , Katja E. Boysen
    • , Jonathan P. Bradfield
    • , Lawrence C. Brody
    • , Russell J. Buono
    • , Ellen Campbell
    • , Gregory D. Cascino
    • , Claudia B. Catarino
    • , Gianpiero L. Cavalleri
    • , Stacey S. Cherny
    • , Krishna Chinthapalli
    • , Alison J. Coffey
    • , Alastair Compston
    • , Antonietta Coppola
    • , Patrick Cossette
    • , John J. Craig
    • , Gerrit-Jan de Haan
    • , Peter De Jonghe
    • , Carolien G. F. de Kovel
    • , Norman Delanty
    • , Chantal Depondt
    • , Orrin Devinsky
    • , Dennis J. Dlugos
    • , Colin P. Doherty
    • , Christian E. Elger
    • , Johan G. Eriksson
    • , Thomas N. Ferraro
    • , Martha Feucht
    • , Ben Francis
    • , Andre Franke
    • , Jacqueline A. French
    • , Saskia Freytag
    • , Verena Gaus
    • , Eric B. Geller
    • , Christian Gieger
    • , Tracy Glauser
    • , Simon Glynn
    • , David B. Goldstein
    • , Hongsheng Gui
    • , Youling Guo
    • , Kevin F. Haas
    • , Hakon Hakonarson
    • , Kerstin Hallmann
    • , Sheryl Haut
    • , Erin L. Heinzen
    • , Ingo Helbig
    • , Christian Hengsbach
    • , Helle Hjalgrim
    • , Michele Iacomino
    • , Andrés Ingason
    • , Jennifer Jamnadas-Khoda
    • , Michael R. Johnson
    • , Reetta Kälviäinen
    • , Anne-Mari Kantanen
    • , Dalia Kasperavičiūte
    • , Dorothee Kasteleijn-Nolst Trenite
    • , Heidi E. Kirsch
    • , Robert C. Knowlton
    • , Bobby P. C. Koeleman
    • , Roland Krause
    • , Martin Krenn
    • , Wolfram S. Kunz
    • , Ruben Kuzniecky
    • , Patrick Kwan
    • , Dennis Lal
    • , Yu-Lung Lau
    • , Anna-Elina Lehesjoki
    • , Holger Lerche
    • , Costin Leu
    • , Wolfgang Lieb
    • , Dick Lindhout
    • , Warren D. Lo
    • , Iscia Lopes-Cendes
    • , Daniel H. Lowenstein
    • , Alberto Malovini
    • , Anthony G. Marson
    • , Thomas Mayer
    • , Mark McCormack
    • , James L. Mills
    • , Nasir Mirza
    • , Martina Moerzinger
    • , Rikke S. Møller
    • , Anne M. Molloy
    • , Hiltrud Muhle
    • , Mark Newton
    • , Ping-Wing Ng
    • , Markus M. Nöthen
    • , Peter Nürnberg
    • , Terence J. O’Brien
    • , Karen L. Oliver
    • , Aarno Palotie
    • , Faith Pangilinan
    • , Sarah Peter
    • , Slavé Petrovski
    • , Annapurna Poduri
    • , Michael Privitera
    • , Rodney Radtke
    • , Sarah Rau
    • , Philipp S. Reif
    • , Eva M. Reinthaler
    • , Felix Rosenow
    • , Josemir W. Sander
    • , Thomas Sander
    • , Theresa Scattergood
    • , Steven C. Schachter
    • , Christoph J. Schankin
    • , Ingrid E. Scheffer
    • , Bettina Schmitz
    • , Susanne Schoch
    • , Pak C. Sham
    • , Jerry J. Shih
    • , Graeme J. Sills
    • , Sanjay M. Sisodiya
    • , Lisa Slattery
    • , Alexander Smith
    • , David F. Smith
    • , Michael C. Smith
    • , Philip E. Smith
    • , Anja C. M. Sonsma
    • , Doug Speed
    • , Michael R. Sperling
    • , Bernhard J. Steinhoff
    • , Ulrich Stephani
    • , Remi Stevelink
    • , Konstantin Strauch
    • , Pasquale Striano
    • , Hans Stroink
    • , Rainer Surges
    • , K. Meng Tan
    • , Liu Lin Thio
    • , G. Neil Thomas
    • , Marian Todaro
    • , Rossana Tozzi
    • , Maria S. Vari
    • , Eileen P. G. Vining
    • , Frank Visscher
    • , Sarah von Spiczak
    • , Nicole M. Walley
    • , Yvonne G. Weber
    • , Zhi Wei
    • , Judith Weisenberg
    • , Christopher D. Whelan
    • , Peter Widdess-Walsh
    • , Markus Wolff
    • , Stefan Wolking
    • , Wanling Yang
    • , Federico Zara
    •  & Fritz Zimprich
  • Article | | open

    Myotonic dystrophy type 1 (DM1) is associated with aberrant transcript splicing. Here, the authors develop a transgenic mouse model expressing a bi-chromatic reporter system that allows non-invasive monitoring of splicing of a transcript altered in DM1 in vivo, and show that it allows for evaluation of the therapeutic response to treatment with antisense oligonucleotides.

    • Ningyan Hu
    • , Layal Antoury
    • , Timothy M. Baran
    • , Soumya Mitra
    • , C. Frank Bennett
    • , Frank Rigo
    • , Thomas H. Foster
    •  & Thurman M. Wheeler
  • Article | | open

    The diagnosis of sleep disorders such as narcolepsy and insomnia currently requires experts to interpret sleep recordings (polysomnography). Here, the authors introduce a neural network analysis method for polysomnography that could reduce time spent in sleep clinics and automate narcolepsy diagnosis.

    • Jens B. Stephansen
    • , Alexander N. Olesen
    • , Mads Olsen
    • , Aditya Ambati
    • , Eileen B. Leary
    • , Hyatt E. Moore
    • , Oscar Carrillo
    • , Ling Lin
    • , Fang Han
    • , Han Yan
    • , Yun L. Sun
    • , Yves Dauvilliers
    • , Sabine Scholz
    • , Lucie Barateau
    • , Birgit Hogl
    • , Ambra Stefani
    • , Seung Chul Hong
    • , Tae Won Kim
    • , Fabio Pizza
    • , Giuseppe Plazzi
    • , Stefano Vandi
    • , Elena Antelmi
    • , Dimitri Perrin
    • , Samuel T. Kuna
    • , Paula K. Schweitzer
    • , Clete Kushida
    • , Paul E. Peppard
    • , Helge B. D. Sorensen
    • , Poul Jennum
    •  & Emmanuel Mignot
  • Article | | open

    A major goal in neuropharmacology is to develop new tools to effectively test the therapeutic potential of pharmacological agents to treat neurological and psychiatric conditions. Here, authors present an in vivo drug screening system that generates large-scale brain activity maps to be used with machine learning to predict the therapeutic potential of clinically relevant drug leads.

    • Xudong Lin
    • , Xin Duan
    • , Claire Jacobs
    • , Jeremy Ullmann
    • , Chung-Yuen Chan
    • , Siya Chen
    • , Shuk-Han Cheng
    • , Wen-Ning Zhao
    • , Annapurna Poduri
    • , Xin Wang
    • , Stephen J. Haggarty
    •  & Peng Shi
  • Article | | open

    In the mdx mouse model of Duchenne muscular dystrophy, muscle contractions lead to force loss, which is attributed to myofibre damage. Here, the authors show that force loss is instead mediated by a redox circuit involving NOX2, PROX1, myoglobin and cytoplasmic actins, and suggest that it may be a protective mechanism to prevent excessive contraction-induced myofibre damage.

    • John T. Olthoff
    • , Angus Lindsay
    • , Reem Abo-Zahrah
    • , Kristen A. Baltgalvis
    • , Xiaobai Patrinostro
    • , Joseph J. Belanto
    • , Dae-Yeul Yu
    • , Benjamin J. Perrin
    • , Daniel J. Garry
    • , George G. Rodney
    • , Dawn A. Lowe
    •  & James M. Ervasti
  • Article | | open

    Myotubular myopathy is a severe muscle disease for which no effective treatment exists. Here, the authors show that tamoxifen ameliorates pathology and extends survival in a mouse model of the disease, and that the effect is mediated via estrogen receptor signaling and involves modulation of DNM2 expression.

    • Nika Maani
    • , Nesrin Sabha
    • , Kamran Rezai
    • , Arun Ramani
    • , Linda Groom
    • , Nadine Eltayeb
    • , Faranak Mavandadnejad
    • , Andrea Pang
    • , Giulia Russo
    • , Michael Brudno
    • , Volker Haucke
    • , Robert T. Dirksen
    •  & James J. Dowling
  • Article | | open

    X-linked myotubular myopathy (XLMTM) is a severe muscle disease with no effective treatment. Here, the authors show that tamoxifen, a drug used to treat breast cancer, rescues the pathology in a mouse model of the disease, at least in part by normalizing expression of the disease modifier proteins DNM2 and BIN1

    • Elinam Gayi
    • , Laurence A. Neff
    • , Xènia Massana Muñoz
    • , Hesham M. Ismail
    • , Marta Sierra
    • , Thomas Mercier
    • , Laurent A. Décosterd
    • , Jocelyn Laporte
    • , Belinda S. Cowling
    • , Olivier M. Dorchies
    •  & Leonardo Scapozza
  • Article | | open

    Mutations in presenilin, which cleaves amyloid precursor protein, cause familial Alzheimer’s Disease. Here, the authors show that loss of presenilin leads to loss of synaptotagmin 7, leading to impaired presynaptic release.

    • Gaël Barthet
    • , Tomàs Jordà-Siquier
    • , Julie Rumi-Masante
    • , Fanny Bernadou
    • , Ulrike Müller
    •  & Christophe Mulle
  • Article | | open

    Brain tumours are associated with epilepsy. Here the authors show, using a mouse model, that the degradation of perineuronal nets around fast spiking interneurons near the tumour contribute to seizures by increasing their membrane capacitance and firing.

    • Bhanu P. Tewari
    • , Lata Chaunsali
    • , Susan L. Campbell
    • , Dipan C. Patel
    • , Adam E. Goode
    •  & Harald Sontheimer
  • Article | | open

    The treatment of brain metastases is often limited by the ability to diagnose their origins. Here the authors generate DNA methylomes from the three most frequent types of brain metastases, identify epigenetic signatures specific to each type of metastasis and construct a DNA methylation-based classifier (BrainMETH) to advance brain metastasis diagnosis.

    • Javier I. J. Orozco
    • , Theo A. Knijnenburg
    • , Ayla O. Manughian-Peter
    • , Matthew P. Salomon
    • , Garni Barkhoudarian
    • , John R. Jalas
    • , James S. Wilmott
    • , Parvinder Hothi
    • , Xiaowen Wang
    • , Yuki Takasumi
    • , Michael E. Buckland
    • , John F. Thompson
    • , Georgina V. Long
    • , Charles S. Cobbs
    • , Ilya Shmulevich
    • , Daniel F. Kelly
    • , Richard A. Scolyer
    • , Dave S. B. Hoon
    •  & Diego M. Marzese
  • Article | | open

    Chromodomain Helicase DNA-binding (CHD) proteins have been implicated in neurodevelopmental processes. Here, the authors identify missense variants in CHD3 that disturb its chromatin remodeling activities and cause a neurodevelopmental disorder with macrocephaly and speech and language impairment.

    • Lot Snijders Blok
    • , Justine Rousseau
    • , Joanna Twist
    • , Sophie Ehresmann
    • , Motoki Takaku
    • , Hanka Venselaar
    • , Lance H. Rodan
    • , Catherine B. Nowak
    • , Jessica Douglas
    • , Kathryn J. Swoboda
    • , Marcie A. Steeves
    • , Inderneel Sahai
    • , Connie T. R. M. Stumpel
    • , Alexander P. A. Stegmann
    • , Patricia Wheeler
    • , Marcia Willing
    • , Elise Fiala
    • , Aaina Kochhar
    • , William T. Gibson
    • , Ana S. A. Cohen
    • , Ruky Agbahovbe
    • , A. Micheil Innes
    • , P. Y. Billie Au
    • , Julia Rankin
    • , Ilse J. Anderson
    • , Steven A. Skinner
    • , Raymond J. Louie
    • , Hannah E. Warren
    • , Alexandra Afenjar
    • , Boris Keren
    • , Caroline Nava
    • , Julien Buratti
    • , Arnaud Isapof
    • , Diana Rodriguez
    • , Raymond Lewandowski
    • , Jennifer Propst
    • , Ton van Essen
    • , Murim Choi
    • , Sangmoon Lee
    • , Jong H. Chae
    • , Susan Price
    • , Rhonda E. Schnur
    • , Ganka Douglas
    • , Ingrid M. Wentzensen
    • , Christiane Zweier
    • , André Reis
    • , Martin G. Bialer
    • , Christine Moore
    • , Marije Koopmans
    • , Eva H. Brilstra
    • , Glen R. Monroe
    • , Koen L. I. van Gassen
    • , Ellen van Binsbergen
    • , Ruth Newbury-Ecob
    • , Lucy Bownass
    • , Ingrid Bader
    • , Johannes A. Mayr
    • , Saskia B. Wortmann
    • , Kathy J. Jakielski
    • , Edythe A. Strand
    • , Katja Kloth
    • , Tatjana Bierhals
    • , John D. Roberts
    • , Robert M. Petrovich
    • , Shinichi Machida
    • , Hitoshi Kurumizaka
    • , Stefan Lelieveld
    • , Rolph Pfundt
    • , Sandra Jansen
    • , Pelagia Deriziotis
    • , Laurence Faive
    • , Julien Thevenon
    • , Mirna Assoum
    • , Lawrence Shriberg
    • , Tjitske Kleefstra
    • , Han G. Brunner
    • , Paul A. Wade
    • , Simon E. Fisher
    •  & Philippe M. Campeau
  • Article | | open

    Previous studies have shown that depletion of microglia at early developmental stages leads to neuronal death. Here the authors use an inducible system to ablate microglia in adulthood, showing that such depletion leads to ataxia-like behavior and neuronal loss, and identifying the inflammatory components that may contribute.

    • Stephen J. Rubino
    • , Lior Mayo
    • , Isabella Wimmer
    • , Victoria Siedler
    • , Florian Brunner
    • , Simon Hametner
    • , Asaf Madi
    • , Amanda Lanser
    • , Thais Moreira
    • , Dustin Donnelly
    • , Laura Cox
    • , Rafael Machado Rezende
    • , Oleg Butovsky
    • , Hans Lassmann
    •  & Howard L. Weiner
  • Article | | open

    The radiation and chemotherapy used for treating medulloblastoma patients cause debilitating side effects. Here, the authors show that miR-584 acts as a therapeutic adjuvant as it sensitizes medulloblastoma to radiation and chemotherapy by targeting HDAC1 or eIF4E3 to enhance spindle defects and DNA damage.

    • Nourhan Abdelfattah
    • , Subapriya Rajamanickam
    • , Subbarayalu Panneerdoss
    • , Santosh Timilsina
    • , Pooja Yadav
    • , Benjamin C. Onyeagucha
    • , Michael Garcia
    • , Ratna Vadlamudi
    • , Yidong Chen
    • , Andrew Brenner
    • , Peter Houghton
    •  & Manjeet K. Rao
  • Article | | open

    Functional peptides can be encoded by short open reading frames in non-coding RNA. Here, the authors identify a 87aa peptide encoded by the circular form of the long intergenic non-protein-coding RNA p53-induced transcript (LINC-PINT) that can reduce glioblastoma proliferation via interaction with PAF1 which sequentially inhibits the transcriptional elongation of some oncogenes.

    • Maolei Zhang
    • , Kun Zhao
    • , Xiaoping Xu
    • , Yibing Yang
    • , Sheng Yan
    • , Ping Wei
    • , Hui Liu
    • , Jianbo Xu
    • , Feizhe Xiao
    • , Huangkai Zhou
    • , Xuesong Yang
    • , Nunu Huang
    • , Jinglei Liu
    • , Kejun He
    • , Keping Xie
    • , Gong Zhang
    • , Suyun Huang
    •  & Nu Zhang
  • Article | | open

    Many brain-injured patients retain large cortical islands that are intact, active and reactive but blocked in a state of low complexity, leading to unconsciousness. Here, the authors show that this loss of complexity is due to the pathological engagement of sleep-like neuronal mechanisms.

    • M. Rosanova
    • , M. Fecchio
    • , S. Casarotto
    • , S. Sarasso
    • , A. G. Casali
    • , A. Pigorini
    • , A. Comanducci
    • , F. Seregni
    • , G. Devalle
    • , G. Citerio
    • , O. Bodart
    • , M. Boly
    • , O. Gosseries
    • , S. Laureys
    •  & M. Massimini
  • Article | | open

    Mutations in pantotenate kinase (PANK) cause neurodegneration. Here the authors carry out achemical screen and identify a PANK activator that is orally available, crosses the blood brain barrierand show that it effecttive in improving pathology and life span in a mouse model of the disease.

    • Lalit Kumar Sharma
    • , Chitra Subramanian
    • , Mi-Kyung Yun
    • , Matthew W. Frank
    • , Stephen W. White
    • , Charles O. Rock
    • , Richard E. Lee
    •  & Suzanne Jackowski
  • Article | | open

    The APOE ε4 allele is a strong genetic risk factor for Alzheimer’s disease, whereas the APOE ε2 allele is protective. Here the authors show that mice expressing the human APOE ε2/ε2 genotype have increased tau pathology and related behavioral deficits; they also find that the APOE ε2 allele is associated with an increased burden of tau pathology in postmortem human brains with progressive supranuclear palsy.

    • Na Zhao
    • , Chia-Chen Liu
    • , Alexandra J. Van Ingelgom
    • , Cynthia Linares
    • , Aishe Kurti
    • , Joshua A. Knight
    • , Michael G. Heckman
    • , Nancy N. Diehl
    • , Mitsuru Shinohara
    • , Yuka A. Martens
    • , Olivia N. Attrebi
    • , Leonard Petrucelli
    • , John D. Fryer
    • , Zbigniew K. Wszolek
    • , Neill R. Graff-Radford
    • , Richard J. Caselli
    • , Monica Y. Sanchez-Contreras
    • , Rosa Rademakers
    • , Melissa E. Murray
    • , Shunsuke Koga
    • , Dennis W. Dickson
    • , Owen A. Ross
    •  & Guojun Bu
  • Article | | open

    Olfaction, the sense of smell, may have originally evolved to aid navigation in space, but there is no direct evidence of a link between olfaction and navigation in humans. Here the authors show that olfaction and spatial memory abilities are correlated and rely on similar brain regions in humans.

    • Louisa Dahmani
    • , Raihaan M. Patel
    • , Yiling Yang
    • , M. Mallar Chakravarty
    • , Lesley K. Fellows
    •  & Véronique D. Bohbot
  • Article | | open

    Nuak1 is an autism spectrum disorder candidate gene. Here the authors report behavioral and cortical development in mice heterozygous for Nuak1, suggesting loss of function mutations in one copy of Nuak1 may contribute to neurodevelopmental disorders.

    • Virginie Courchet
    • , Amanda J. Roberts
    • , Géraldine Meyer-Dilhet
    • , Peggy Del Carmine
    • , Tommy L. Lewis Jr
    • , Franck Polleux
    •  & Julien Courchet
  • Article | | open

    Progressive diseases tend to be heterogeneous in their underlying aetiology mechanism, disease manifestation, and disease time course. Here, Young and colleagues devise a computational method to account for both phenotypic heterogeneity and temporal heterogeneity, and demonstrate it using two neurodegenerative disease cohorts.

    • Alexandra L Young
    • , Razvan V Marinescu
    • , Neil P Oxtoby
    • , Martina Bocchetta
    • , Keir Yong
    • , Nicholas C Firth
    • , David M Cash
    • , David L Thomas
    • , Katrina M Dick
    • , Jorge Cardoso
    • , John van Swieten
    • , Barbara Borroni
    • , Daniela Galimberti
    • , Mario Masellis
    • , Maria Carmela Tartaglia
    • , James B Rowe
    • , Caroline Graff
    • , Fabrizio Tagliavini
    • , Giovanni B Frisoni
    • , Robert Laforce Jr
    • , Elizabeth Finger
    • , Alexandre de Mendonça
    • , Sandro Sorbi
    • , Jason D Warren
    • , Sebastian Crutch
    • , Nick C Fox
    • , Sebastien Ourselin
    • , Jonathan M Schott
    • , Jonathan D Rohrer
    • , Daniel C Alexander
    • , Christin Andersson
    • , Silvana Archetti
    • , Andrea Arighi
    • , Luisa Benussi
    • , Giuliano Binetti
    • , Sandra Black
    • , Maura Cosseddu
    • , Marie Fallström
    • , Carlos Ferreira
    • , Chiara Fenoglio
    • , Morris Freedman
    • , Giorgio G Fumagalli
    • , Stefano Gazzina
    • , Roberta Ghidoni
    • , Marina Grisoli
    • , Vesna Jelic
    • , Lize Jiskoot
    • , Ron Keren
    • , Gemma Lombardi
    • , Carolina Maruta
    • , Lieke Meeter
    • , Simon Mead
    • , Rick van Minkelen
    • , Benedetta Nacmias
    • , Linn Öijerstedt
    • , Alessandro Padovani
    • , Jessica Panman
    • , Michela Pievani
    • , Cristina Polito
    • , Enrico Premi
    • , Sara Prioni
    • , Rosa Rademakers
    • , Veronica Redaelli
    • , Ekaterina Rogaeva
    • , Giacomina Rossi
    • , Martin Rossor
    • , Elio Scarpini
    • , David Tang-Wai
    • , Hakan Thonberg
    • , Pietro Tiraboschi
    • , Ana Verdelho
    • , Michael W Weiner
    • , Paul Aisen
    • , Ronald Petersen
    • , Clifford R Jack
    • , William Jagust
    • , John Q Trojanowki
    • , Arthur W Toga
    • , Laurel Beckett
    • , Robert C Green
    • , Andrew J Saykin
    • , John Morris
    • , Leslie M Shaw
    • , Zaven Khachaturian
    • , Greg Sorensen
    • , Lew Kuller
    • , Marc Raichle
    • , Steven Paul
    • , Peter Davies
    • , Howard Fillit
    • , Franz Hefti
    • , Davie Holtzman
    • , M Marcel Mesulam
    • , William Potter
    • , Peter Snyder
    • , Adam Schwartz
    • , Tom Montine
    • , Ronald G Thomas
    • , Michael Donohue
    • , Sarah Walter
    • , Devon Gessert
    • , Tamie Sather
    • , Gus Jiminez
    • , Danielle Harvey
    • , Matthew Bernstein
    • , Paul Thompson
    • , Norbert Schuff
    • , Bret Borowski
    • , Jeff Gunter
    • , Matt Senjem
    • , Prashanthi Vemuri
    • , David Jones
    • , Kejal Kantarci
    • , Chad Ward
    • , Robert A Koeppe
    • , Norm Foster
    • , Eric M Reiman
    • , Kewei Chen
    • , Chet Mathis
    • , Susan Landau
    • , Nigel J Cairns
    • , Erin Householder
    • , Lisa Taylor-Reinwald
    • , Virginia Lee
    • , Magdalena Korecka
    • , Michal Figurski
    • , Karen Crawford
    • , Scott Neu
    • , Tatiana M Foroud
    • , Steven Potkin
    • , Li Shen
    • , Kelley Faber
    • , Sungeun Kim
    • , Kwangsik Nho
    • , Leon Thal
    • , Neil Buckholtz
    • , Marylyn Albert
    • , Richard Frank
    • , John Hsiao
    • , Jeffrey Kaye
    • , Joseph Quinn
    • , Betty Lind
    • , Raina Carter
    • , Sara Dolen
    • , Lon S Schneider
    • , Sonia Pawluczyk
    • , Mauricio Beccera
    • , Liberty Teodoro
    • , Bryan M Spann
    • , James Brewer
    • , Helen Vanderswag
    • , Adam Fleisher
    • , Judith L Heidebrink
    • , Joanne L Lord
    • , Sara S Mason
    • , Colleen S Albers
    • , David Knopman
    • , Kris Johnson
    • , Rachelle S Doody
    • , Javier Villanueva-Meyer
    • , Munir Chowdhury
    • , Susan Rountree
    • , Mimi Dang
    • , Yaakov Stern
    • , Lawrence S Honig
    • , Karen L Bell
    • , Beau Ances
    • , Maria Carroll
    • , Sue Leon
    • , Mark A Mintun
    • , Stacy Schneider
    • , Angela Oliver
    • , Daniel Marson
    • , Randall Griffith
    • , David Clark
    • , David Geldmacher
    • , John Brockington
    • , Erik Roberson
    • , Hillel Grossman
    • , Effie Mitsis
    • , Leyla de Toledo-Morrell
    • , Raj C Shah
    • , Ranjan Duara
    • , Daniel Varon
    • , Maria T Greig
    • , Peggy Roberts
    • , Marilyn Albert
    • , Chiadi Onyike
    • , Daniel D’Agostino
    • , Stephanie Kielb
    • , James E Galvin
    • , Brittany Cerbone
    • , Christina A Michel
    • , Henry Rusinek
    • , Mony J de Leon
    • , Lidia Glodzik
    • , Susan De Santi
    • , P Murali Doraiswamy
    • , Jeffrey R Petrella
    • , Terence Z Wong
    • , Steven E Arnold
    • , Jason H Karlawish
    • , David Wolk
    • , Charles D Smith
    • , Greg Jicha
    • , Peter Hardy
    • , Partha Sinha
    • , Elizabeth Oates
    • , Gary Conrad
    • , Oscar L Lopez
    • , MaryAnn Oakley
    • , Donna M Simpson
    • , Anton P Porsteinsson
    • , Bonnie S Goldstein
    • , Kim Martin
    • , Kelly M Makino
    • , M Saleem Ismail
    • , Connie Brand
    • , Ruth A Mulnard
    • , Gaby Thai
    • , Catherine Mc-Adams-Ortiz
    • , Kyle Womack
    • , Dana Mathews
    • , Mary Quiceno
    • , Ramon Diaz-Arrastia
    • , Richard King
    • , Myron Weiner
    • , Kristen Martin-Cook
    • , Michael DeVous
    • , Allan I Levey
    • , James J Lah
    • , Janet S Cellar
    • , Jeffrey M Burns
    • , Heather S Anderson
    • , Russell H Swerdlow
    • , Liana Apostolova
    • , Kathleen Tingus
    • , Ellen Woo
    • , Daniel Hs Silverman
    • , Po H Lu
    • , George Bartzokis
    • , Neill R Graff-Radford
    • , Francine Parfitt
    • , Tracy Kendall
    • , Heather Johnson
    • , Martin R Farlow
    • , Ann Marie Hake
    • , Brandy R Matthews
    • , Scott Herring
    • , Cynthia Hunt
    • , Christopher H van Dyck
    • , Richard E Carson
    • , Martha G MacAvoy
    • , Howard Chertkow
    • , Howard Bergman
    • , Chris Hosein
    • , Bojana Stefanovic
    • , Curtis Caldwell
    • , Ging-Yuek Robin Hsiung
    • , Howard Feldman
    • , Benita Mudge
    • , Michele Assaly
    • , Andrew Kertesz
    • , John Rogers
    • , Charles Bernick
    • , Donna Munic
    • , Diana Kerwin
    • , Marek-Marsel Mesulam
    • , Kristine Lipowski
    • , Chuang-Kuo Wu
    • , Nancy Johnson
    • , Carl Sadowsky
    • , Walter Martinez
    • , Teresa Villena
    • , Raymond Scott Turner
    • , Kathleen Johnson
    • , Brigid Reynolds
    • , Reisa A Sperling
    • , Keith A Johnson
    • , Gad Marshall
    • , Meghan Frey
    • , Barton Lane
    • , Allyson Rosen
    • , Jared Tinklenberg
    • , Marwan N Sabbagh
    • , Christine M Belden
    • , Sandra A Jacobson
    • , Sherye A Sirrel
    • , Neil Kowall
    • , Ronald Killiany
    • , Andrew E Budson
    • , Alexander Norbash
    • , Patricia Lynn Johnson
    • , Joanne Allard
    • , Alan Lerner
    • , Paula Ogrocki
    • , Leon Hudson
    • , Evan Fletcher
    • , Owen Carmichael
    • , John Olichney
    • , Charles DeCarli
    • , Smita Kittur
    • , Michael Borrie
    • , T-Y Lee
    • , Rob Bartha
    • , Sterling Johnson
    • , Sanjay Asthana
    • , Cynthia M Carlsson
    • , Steven G Potkin
    • , Adrian Preda
    • , Dana Nguyen
    • , Pierre Tariot
    • , Stephanie Reeder
    • , Vernice Bates
    • , Horacio Capote
    • , Michelle Rainka
    • , Douglas W Scharre
    • , Maria Kataki
    • , Anahita Adeli
    • , Earl A Zimmerman
    • , Dzintra Celmins
    • , Alice D Brown
    • , Godfrey D Pearlson
    • , Karen Blank
    • , Karen Anderson
    • , Robert B Santulli
    • , Tamar J Kitzmiller
    • , Eben S Schwartz
    • , Kaycee M Sink
    • , Jeff D Williamson
    • , Pradeep Garg
    • , Franklin Watkins
    • , Brian R Ott
    • , Henry Querfurth
    • , Geoffrey Tremont
    • , Stephen Salloway
    • , Paul Malloy
    • , Stephen Correia
    • , Howard J Rosen
    • , Bruce L Miller
    • , Jacobo Mintzer
    • , Kenneth Spicer
    • , David Bachman
    • , Stephen Pasternak
    • , Irina Rachinsky
    • , Dick Drost
    • , Nunzio Pomara
    • , Raymundo Hernando
    • , Antero Sarrael
    • , Susan K Schultz
    • , Laura L Boles Ponto
    • , Hyungsub Shim
    • , Karen Elizabeth Smith
    • , Norman Relkin
    • , Gloria Chaing
    • , Lisa Raudin
    • , Amanda Smith
    • , Kristin Fargher
    • , Balebail Ashok Raj
    • , Thomas Neylan
    • , Jordan Grafman
    • , Melissa Davis
    • , Rosemary Morrison
    • , Jacqueline Hayes
    • , Shannon Finley
    • , Karl Friedl
    • , Debra Fleischman
    • , Konstantinos Arfanakis
    • , Olga James
    • , Dino Massoglia
    • , J Jay Fruehling
    • , Sandra Harding
    • , Elaine R Peskind
    • , Eric C Petrie
    • , Gail Li
    • , Jerome A Yesavage
    • , Joy L Taylor
    •  & Ansgar J Furst
  • Article | | open

    Cognitive decline in Huntington’s disease (HD) may be due to impaired hippocampal synaptic plasticity. In this study the authors show that AMPA receptor surface diffusion, a key player in synaptic plasticity, is deregulated in multiple HD mouse models as a result of impaired BDNF signalling that underlies the memory deficits, and can be pharmacologically rescued.

    • Hongyu Zhang
    • , Chunlei Zhang
    • , Jean Vincent
    • , Diana Zala
    • , Caroline Benstaali
    • , Matthieu Sainlos
    • , Dolors Grillo-Bosch
    • , Sophie Daburon
    • , Françoise Coussen
    • , Yoon Cho
    • , Denis J. David
    • , Frederic Saudou
    • , Yann Humeau
    •  & Daniel Choquet
  • Article | | open

    Similar to cancers, somatic mutations might lead to neurodegenerative diseases. Here, the authors perform ultra-deep sequencing of 102 genes in 173 adult human brains, detect somatic mutations in 54 brains, and develop a mathematical model to estimate the frequency of mutated foci in human brains.

    • Michael J. Keogh
    • , Wei Wei
    • , Juvid Aryaman
    • , Lauren Walker
    • , Jelle van den Ameele
    • , Jon Coxhead
    • , Ian Wilson
    • , Matthew Bashton
    • , Jon Beck
    • , John West
    • , Richard Chen
    • , Christian Haudenschild
    • , Gabor Bartha
    • , Shujun Luo
    • , Chris M. Morris
    • , Nick S. Jones
    • , Johannes Attems
    •  & Patrick F. Chinnery
  • Article | | open

    Cell-to-cell transmission of TDP43 occurs in cell cultures and may contribute to pathological TDP43 propagation in FTLD-TDP. In this study, the authors demonstrate using mouse models that a single intracerebral injection of human brain-derived pathological TDP43 from FTLD-TDP cases initiates the process of seeding and spreading of TDP43 pathology in a spatio-temporal dependent manner in the brain.

    • Sílvia Porta
    • , Yan Xu
    • , Clark R. Restrepo
    • , Linda K. Kwong
    • , Bin Zhang
    • , Hannah J. Brown
    • , Edward B. Lee
    • , John Q. Trojanowski
    •  & Virginia M.-Y. Lee
  • Article | | open

    miR-34 is known to regulate age-related gene expression in the Drosophila brain, and miR-34 overexpression can attenuate neurodegeneration induced by polyQ-expanded proteins. Here, Kennerdell and colleagues show that miR-34 confers longevity and neuroprotection via an epigenetic regulator Polycomb Repressive Complex 2 and molecular chaperone expression.

    • Jason R. Kennerdell
    • , Nan Liu
    •  & Nancy M. Bonini
  • Article | | open

    Demyelination failure in multiple sclerosis (MS) may contribute to the disease progression. This study shows that chondroitin sulfate proteoglycans (CSPGs) can inhibit remyelination in an animal model of MS via CSPG binding with the receptor PTPσ on oligodendrocyte progenitor cells, and disruption of this interaction can promote recovery in the animal models of MS.

    • Fucheng Luo
    • , Amanda Phuong Tran
    • , Li Xin
    • , Chandrika Sanapala
    • , Bradley T. Lang
    • , Jerry Silver
    •  & Yan Yang
  • Article | | open

    Group 3 medulloblastoma is an aggressive pediatric brain tumour that disseminates through the leptomeningeal cerebral spinal fluid. Here, the authors show that in Group 3 medulloblastoma NOTCH1 activates BMI1 through the activation of TWIST1, driving metastasis and self-renewal, and in mouse models a NOTCH1 blocking antibody decreased spinal metastases.

    • Suzana A. Kahn
    • , Xin Wang
    • , Ryan T. Nitta
    • , Sharareh Gholamin
    • , Johanna Theruvath
    • , Gregor Hutter
    • , Tej D. Azad
    • , Lina Wadi
    • , Sara Bolin
    • , Vijay Ramaswamy
    • , Rogelio Esparza
    • , Kun-Wei Liu
    • , Michael Edwards
    • , Fredrik J. Swartling
    • , Debashis Sahoo
    • , Gordon Li
    • , Robert J. Wechsler-Reya
    • , Jüri Reimand
    • , Yoon-Jae Cho
    • , Michael D. Taylor
    • , Irving L. Weissman
    • , Siddhartha S. Mitra
    •  & Samuel H. Cheshier
  • Article | | open

    Dopamine tightly regulates plasticity at corticostriatal synapses. Here, the authors report that endocannabinoid dependent LTP induced with few spikes in the striatum is impaired in a rodent model of Parkinson’s disease, requires dopamine through presynaptic D2 receptors located on corticostriatal inputs.

    • Hao Xu
    • , Sylvie Perez
    • , Amandine Cornil
    • , Bérangère Detraux
    • , Ilya Prokin
    • , Yihui Cui
    • , Bertrand Degos
    • , Hugues Berry
    • , Alban de Kerchove d’Exaerde
    •  & Laurent Venance