Neurology

  • Article
    | Open Access

    The exact molecular mechanisms driving FUS-mediated toxicity remain unclear. Here, the authors demonstrate that muscleblind (Mbl) is a novel modifier of FUS-associated ALS, with knockdown of endogenous Mbl suppressing neuromuscular junction defects and motor dysfunctions associated with FUS expression in Drosophila, as well as restoring reduced SMN protein levels in mammalian neuronal and human iPSC-derived motor neurons.

    • Ian Casci
    • , Karthik Krishnamurthy
    • , Sukhleen Kour
    • , Vadreenath Tripathy
    • , Nandini Ramesh
    • , Eric N. Anderson
    • , Lara Marrone
    • , Rogan A. Grant
    • , Stacie Oliver
    • , Lauren Gochenaur
    • , Krishani Patel
    • , Jared Sterneckert
    • , Amanda M. Gleixner
    • , Christopher J. Donnelly
    • , Marc-David Ruepp
    • , Antonella M. Sini
    • , Emanuela Zuccaro
    • , Maria Pennuto
    • , Piera Pasinelli
    •  & Udai Bhan Pandey
  • Article
    | Open Access

    Mutations in LRRK2 and GBA1, which encodes glucocerebrosidase (GCase), are associated with Parkinson’s disease. Here the authors show that LRRK2 is a negative regulator of lysosomal GCase activity, using dopaminergic neurons derived from iPSCs from PD patients with LRRK2 mutations.

    • Daniel Ysselstein
    • , Maria Nguyen
    • , Tiffany J. Young
    • , Alex Severino
    • , Michael Schwake
    • , Kalpana Merchant
    •  & Dimitri Krainc
  • Article
    | Open Access

    Siblings of those with autism spectrum disorder (ASD) have increased likelihood of ASD or related subclinical traits. Here, studying 253 ASD families, D’Abate et al. test the predictive value of genomic copy number variation involving ASD-associated loci, with confirmation in a second cohort.

    • L. D’Abate
    • , S. Walker
    • , R. K. C. Yuen
    • , K. Tammimies
    • , J. A. Buchanan
    • , R. W. Davies
    • , B. Thiruvahindrapuram
    • , J. Wei
    • , J. Brian
    • , S. E. Bryson
    • , K. Dobkins
    • , J. Howe
    • , R. Landa
    • , J. Leef
    • , D. Messinger
    • , S. Ozonoff
    • , I. M. Smith
    • , W. L. Stone
    • , Z. E. Warren
    • , G. Young
    • , L. Zwaigenbaum
    •  & S. W. Scherer
  • Article
    | Open Access

    Parkinson’s disease (PD) and Multiple System Atrophy (MSA) are characterized by the pathological accumulation of α-synuclein. Here the authors employ fluorescent probes, electron microscopy and NMR spectroscopy to study the properties of α-synuclein aggregates that were amplified from patient brain extracts and observe a greater structural diversity among PD patients compared to MSA patients.

    • Timo Strohäker
    • , Byung Chul Jung
    • , Shu-Hao Liou
    • , Claudio O. Fernandez
    • , Dietmar Riedel
    • , Stefan Becker
    • , Glenda M. Halliday
    • , Marina Bennati
    • , Woojin S. Kim
    • , Seung-Jae Lee
    •  & Markus Zweckstetter
  • Article
    | Open Access

    Many approaches exist to process data from individual imaging modalities, but integrating them is challenging. The authors develop an automated resource that enables co-registered network- and tract-level analysis of macroscopic in-vivo imaging and microscopic imaging of cleared tissue.

    • Maged Goubran
    • , Christoph Leuze
    • , Brian Hsueh
    • , Markus Aswendt
    • , Li Ye
    • , Qiyuan Tian
    • , Michelle Y. Cheng
    • , Ailey Crow
    • , Gary K. Steinberg
    • , Jennifer A. McNab
    • , Karl Deisseroth
    •  & Michael Zeineh
  • Article
    | Open Access

    Mechanisms of transcription of expanded G4C2 repeats in C9ORF72, associated with ALS/FTD, are not fully understood. Here authors use both Drosophila and C9ORF72 iPSC-derived neurons and identify AFF2/FMR2 as a regulator of poly(GR) toxicity by regulating expression of the expanded G4C2 repeats.

    • Yeliz Yuva-Aydemir
    • , Sandra Almeida
    • , Gopinath Krishnan
    • , Tania F. Gendron
    •  & Fen-Biao Gao
  • Article
    | Open Access

    Slow gamma oscillations are associated with memory and have been reported to be disrupted in patients with Alzheimer’s disease. Here the authors show that optogenetic stimulation of medial septum parvalbumin neurons at 40 Hz rescues memory retrieval in the J20 mouse model of Alzheimer’s disease.

    • Guillaume Etter
    • , Suzanne van der Veldt
    • , Frédéric Manseau
    • , Iman Zarrinkoub
    • , Emilie Trillaud-Doppia
    •  & Sylvain Williams
  • Article
    | Open Access

    Parkinson’s disease (PD) is characterized by neurodegeneration associated with loss of dopaminergic (DA) neurons and deposition of Lewy bodies. Here, Wang et al. use co-expression network analysis to pinpoint disease pathways and propose reduced expression of STMN2 as a cause of presynaptic function loss in PD.

    • Qian Wang
    • , Yuanxi Zhang
    • , Minghui Wang
    • , Won-Min Song
    • , Qi Shen
    • , Andrew McKenzie
    • , Insup Choi
    • , Xianxiao Zhou
    • , Ping-Yue Pan
    • , Zhenyu Yue
    •  & Bin Zhang
  • Article
    | Open Access

    T cells from narcolepsy patients were recently reported to recognize hypocretin, a wakefulness-promoting neurohormone, suggesting autoimmune origin of the disease. Here the authors show that hypocretin-specific T cells expand both in healthy controls and in narcolepsy patients, and identify preliminary features that may distinguish them.

    • Wei Jiang
    • , James R. Birtley
    • , Shu-Chen Hung
    • , Weiqi Wang
    • , Shin-Heng Chiou
    • , Claudia Macaubas
    • , Birgitte Kornum
    • , Lu Tian
    • , Huang Huang
    • , Lital Adler
    • , Grant Weaver
    • , Liying Lu
    • , Alexandra Ilstad-Minnihan
    • , Sriram Somasundaram
    • , Sashi Ayyangar
    • , Mark M. Davis
    • , Lawrence J. Stern
    •  & Elizabeth D. Mellins
  • Article
    | Open Access

    There is a need to further improve the efficacy of biodegradable wafers used in surgically treated brain tumors. Here, the authors report a flexible, biodegradable wireless device capable of adhesion to surgical site for optimal drug delivery upon mild-thermic actuation and report therapeutic efficacy in mouse and canine tumor models.

    • Jongha Lee
    • , Hye Rim Cho
    • , Gi Doo Cha
    • , Hyunseon Seo
    • , Seunghyun Lee
    • , Chul-Kee Park
    • , Jin Wook Kim
    • , Shutao Qiao
    • , Liu Wang
    • , Dayoung Kang
    • , Taegyu Kang
    • , Tomotsugu Ichikawa
    • , Jonghoon Kim
    • , Hakyong Lee
    • , Woongchan Lee
    • , Sanghoek Kim
    • , Soon-Tae Lee
    • , Nanshu Lu
    • , Taeghwan Hyeon
    • , Seung Hong Choi
    •  & Dae-Hyeong Kim
  • Article
    | Open Access

    The risk of fatal stroke is increased in children, adolescent, and young (<40 years) cancer patients after diagnosis. Here, the authors report a retrospective, population-based study and show that the risk of stroke among cancer patients is twice that of the general population and rises with longer follow up time.

    • Nicholas G. Zaorsky
    • , Ying Zhang
    • , Leila T. Tchelebi
    • , Heath B. Mackley
    • , Vernon M. Chinchilli
    •  & Brad E. Zacharia
  • Article
    | Open Access

    The brain’s capacity to produce new neurons in response to injury is limited. Here, the authors transplant GABAergic progenitor cells and show that they synaptically incorporate into the damaged hippocampus and rescue memory problems and post-traumatic seizures caused by traumatic brain injury.

    • Bingyao Zhu
    • , Jisu Eom
    •  & Robert F. Hunt
  • Article
    | Open Access

    Changes in brain structure asymmetry have been reported in autism spectrum disorder. Here the authors investigate this issue using a large-scale sample consisting of 54 data sets.

    • Merel C. Postema
    • , Daan van Rooij
    • , Evdokia Anagnostou
    • , Celso Arango
    • , Guillaume Auzias
    • , Marlene Behrmann
    • , Geraldo Busatto Filho
    • , Sara Calderoni
    • , Rosa Calvo
    • , Eileen Daly
    • , Christine Deruelle
    • , Adriana Di Martino
    • , Ilan Dinstein
    • , Fabio Luis S. Duran
    • , Sarah Durston
    • , Christine Ecker
    • , Stefan Ehrlich
    • , Damien Fair
    • , Jennifer Fedor
    • , Xin Feng
    • , Jackie Fitzgerald
    • , Dorothea L. Floris
    • , Christine M. Freitag
    • , Louise Gallagher
    • , David C. Glahn
    • , Ilaria Gori
    • , Shlomi Haar
    • , Liesbeth Hoekstra
    • , Neda Jahanshad
    • , Maria Jalbrzikowski
    • , Joost Janssen
    • , Joseph A. King
    • , Xiang Zhen Kong
    • , Luisa Lazaro
    • , Jason P. Lerch
    • , Beatriz Luna
    • , Mauricio M. Martinho
    • , Jane McGrath
    • , Sarah E. Medland
    • , Filippo Muratori
    • , Clodagh M. Murphy
    • , Declan G. M. Murphy
    • , Kirsten O’Hearn
    • , Bob Oranje
    • , Mara Parellada
    • , Olga Puig
    • , Alessandra Retico
    • , Pedro Rosa
    • , Katya Rubia
    • , Devon Shook
    • , Margot J. Taylor
    • , Michela Tosetti
    • , Gregory L. Wallace
    • , Fengfeng Zhou
    • , Paul M. Thompson
    • , Simon E. Fisher
    • , Jan K. Buitelaar
    •  & Clyde Francks
  • Article
    | Open Access

    Familial cortical myoclonic tremor (FAME) has so far been mapped to regions on chromosome 2, 3, 5 and 8 and pentameric repeat expansions in SAMD12 were identified as cause of FAME1. Here, Corbett et al. identify ATTTT/ATTTC repeat expansions in intron 1 of STARD7 in individuals with FAME2.”

    • Mark A. Corbett
    • , Thessa Kroes
    • , Liana Veneziano
    • , Mark F. Bennett
    • , Rahel Florian
    • , Amy L. Schneider
    • , Antonietta Coppola
    • , Laura Licchetta
    • , Silvana Franceschetti
    • , Antonio Suppa
    • , Aaron Wenger
    • , Davide Mei
    • , Manuela Pendziwiat
    • , Sabine Kaya
    • , Massimo Delledonne
    • , Rachel Straussberg
    • , Luciano Xumerle
    • , Brigid Regan
    • , Douglas Crompton
    • , Anne-Fleur van Rootselaar
    • , Anthony Correll
    • , Rachael Catford
    • , Francesca Bisulli
    • , Shreyasee Chakraborty
    • , Sara Baldassari
    • , Paolo Tinuper
    • , Kirston Barton
    • , Shaun Carswell
    • , Martin Smith
    • , Alfredo Berardelli
    • , Renee Carroll
    • , Alison Gardner
    • , Kathryn L. Friend
    • , Ilan Blatt
    • , Michele Iacomino
    • , Carlo Di Bonaventura
    • , Salvatore Striano
    • , Julien Buratti
    • , Boris Keren
    • , Caroline Nava
    • , Sylvie Forlani
    • , Gabrielle Rudolf
    • , Edouard Hirsch
    • , Eric Leguern
    • , Pierre Labauge
    • , Simona Balestrini
    • , Josemir W. Sander
    • , Zaid Afawi
    • , Ingo Helbig
    • , Hiroyuki Ishiura
    • , Shoji Tsuji
    • , Sanjay M. Sisodiya
    • , Giorgio Casari
    • , Lynette G. Sadleir
    • , Riaan van Coller
    • , Marina A. J. Tijssen
    • , Karl Martin Klein
    • , Arn M. J. M. van den Maagdenberg
    • , Federico Zara
    • , Renzo Guerrini
    • , Samuel F. Berkovic
    • , Tommaso Pippucci
    • , Laura Canafoglia
    • , Melanie Bahlo
    • , Pasquale Striano
    • , Ingrid E. Scheffer
    • , Francesco Brancati
    • , Christel Depienne
    •  & Jozef Gecz
  • Article
    | Open Access

    Familial cortical myoclonic tremor with epilepsy (FAME) is a slowly progressing cortical tremor mapping to various genomic loci, including intronic expansions in SAMD12 for FAME1. Here, Florian et al. describe mixed intronic TTTTA/TTTCA expansions of various lengths in the first intron of MARCH6 as a cause of FAME3.

    • Rahel T. Florian
    • , Florian Kraft
    • , Elsa Leitão
    • , Sabine Kaya
    • , Stephan Klebe
    • , Eloi Magnin
    • , Anne-Fleur van Rootselaar
    • , Julien Buratti
    • , Theresa Kühnel
    • , Christopher Schröder
    • , Sebastian Giesselmann
    • , Nikolai Tschernoster
    • , Janine Altmueller
    • , Anaide Lamiral
    • , Boris Keren
    • , Caroline Nava
    • , Delphine Bouteiller
    • , Sylvie Forlani
    • , Ludmila Jornea
    • , Regina Kubica
    • , Tao Ye
    • , Damien Plassard
    • , Bernard Jost
    • , Vincent Meyer
    • , Jean-François Deleuze
    • , Yannick Delpu
    • , Mario D. M. Avarello
    • , Lisanne S. Vijfhuizen
    • , Gabrielle Rudolf
    • , Edouard Hirsch
    • , Thessa Kroes
    • , Philipp S. Reif
    • , Felix Rosenow
    • , Christos Ganos
    • , Marie Vidailhet
    • , Lionel Thivard
    • , Alexandre Mathieu
    • , Thomas Bourgeron
    • , Ingo Kurth
    • , Haloom Rafehi
    • , Laura Steenpass
    • , Bernhard Horsthemke
    • , Samuel F. Berkovic
    • , Francesca Bisulli
    • , Francesco Brancati
    • , Laura Canafoglia
    • , Giorgio Casari
    • , Renzo Guerrini
    • , Hiroyuki Ishiura
    • , Laura Licchetta
    • , Davide Mei
    • , Tommaso Pippucci
    • , Lynette Sadleir
    • , Ingrid E. Scheffer
    • , Pasquale Striano
    • , Paolo Tinuper
    • , Shoji Tsuji
    • , Federico Zara
    • , Eric LeGuern
    • , Karl Martin Klein
    • , Pierre Labauge
    • , Mark F. Bennett
    • , Melanie Bahlo
    • , Jozef Gecz
    • , Mark A. Corbett
    • , Marina A. J. Tijssen
    • , Arn M. J. M. van den Maagdenberg
    •  & Christel Depienne
  • Article
    | Open Access

    Alzheimer’s disease is characterised by the deposition of Aβ amyloid fibrils and tau protein neurofibrillary tangles. Here the authors use cryo-EM to structurally characterise brain derived Aβ amyloid fibrils and find that they are polymorphic and right-hand twisted, which differs from in vitro generated Aβ fibrils.

    • Marius Kollmer
    • , William Close
    • , Leonie Funk
    • , Jay Rasmussen
    • , Aref Bsoul
    • , Angelika Schierhorn
    • , Matthias Schmidt
    • , Christina J. Sigurdson
    • , Mathias Jucker
    •  & Marcus Fändrich
  • Article
    | Open Access

    Mitofusin-2 (MFN2) is a dynamin-like GTPase that plays a central role in regulating mitochondrial fusion and cell metabolism. Here, authors report crystal structures of truncated human MFN2 in different nucleotide-loading states and show that MFN2 forms sustained dimers even after GTP hydrolysis.

    • Yu-Jie Li
    • , Yu-Lu Cao
    • , Jian-Xiong Feng
    • , Yuanbo Qi
    • , Shuxia Meng
    • , Jie-Feng Yang
    • , Ya-Ting Zhong
    • , Sisi Kang
    • , Xiaoxue Chen
    • , Lan Lan
    • , Li Luo
    • , Bing Yu
    • , Shoudeng Chen
    • , David C. Chan
    • , Junjie Hu
    •  & Song Gao
  • Article
    | Open Access

    Deposition of tau protein aggregates occurs during aging and Alzheimer disease. Here, the authors show that tau burden in the anterior-temporal memory network is associated with disrupted fMRI connectivity and functional isolation of the hippocampus from other memory network components.

    • Theresa M. Harrison
    • , Anne Maass
    • , Jenna N. Adams
    • , Richard Du
    • , Suzanne L. Baker
    •  & William J. Jagust
  • Article
    | Open Access

    Food intake shapes intestinal microbiome composition, which in turn shapes adaptive immune responses. Here the authors show that dietary tryptophan restriction (DTR) protects mice from subsequent autoimmune neuropathology challenge by altering intestinal microbiota, highlighting the potential of diet-regulated microbiota to prevent immune pathology.

    • Jana K. Sonner
    • , Melanie Keil
    • , Maren Falk-Paulsen
    • , Neha Mishra
    • , Ateequr Rehman
    • , Magdalena Kramer
    • , Katrin Deumelandt
    • , Julian Röwe
    • , Khwab Sanghvi
    • , Lara Wolf
    • , Anna von Landenberg
    • , Hendrik Wolff
    • , Richa Bharti
    • , Iris Oezen
    • , Tobias V. Lanz
    • , Florian Wanke
    • , Yilang Tang
    • , Ines Brandao
    • , Soumya R. Mohapatra
    • , Lisa Epping
    • , Alexandra Grill
    • , Ralph Röth
    • , Beate Niesler
    • , Sven G. Meuth
    • , Christiane A. Opitz
    • , Jürgen G. Okun
    • , Christoph Reinhardt
    • , Florian C. Kurschus
    • , Wolfgang Wick
    • , Helge B. Bode
    • , Philip Rosenstiel
    •  & Michael Platten
  • Article
    | Open Access

    Disturbances in IP3 receptor-mediated release of Ca2+ from the endoplasmatic reticulum are associated with neurodegenerative disease. Here, the authors identify in four families with hereditary spastic paraplegia biallelic mutations in RNF170 that associate with increased basal levels of IP3 receptors.

    • Matias Wagner
    • , Daniel P. S. Osborn
    • , Ina Gehweiler
    • , Maike Nagel
    • , Ulrike Ulmer
    • , Somayeh Bakhtiari
    • , Rim Amouri
    • , Reza Boostani
    • , Faycal Hentati
    • , Maryam M. Hockley
    • , Benedikt Hölbling
    • , Thomas Schwarzmayr
    • , Ehsan Ghayoor Karimiani
    • , Christoph Kernstock
    • , Reza Maroofian
    • , Wolfgang Müller-Felber
    • , Ege Ozkan
    • , Sergio Padilla-Lopez
    • , Selina Reich
    • , Jennifer Reichbauer
    • , Hossein Darvish
    • , Neda Shahmohammadibeni
    • , Abbas Tafakhori
    • , Katharina Vill
    • , Stephan Zuchner
    • , Michael C. Kruer
    • , Juliane Winkelmann
    • , Yalda Jamshidi
    •  & Rebecca Schüle
  • Article
    | Open Access

    Neurodevelopmental disorders (NDDs) are a heterogeneous group of diseases for which the genetic basis is still unknown in more than half of the cases. Here, the authors report a NDD associated with disruptive variants in the TANC2 gene and show that rols, the TANC2 homolog in flies, is required for synapse growth and function.

    • Hui Guo
    • , Elisa Bettella
    • , Paul C. Marcogliese
    • , Rongjuan Zhao
    • , Jonathan C. Andrews
    • , Tomasz J. Nowakowski
    • , Madelyn A. Gillentine
    • , Kendra Hoekzema
    • , Tianyun Wang
    • , Huidan Wu
    • , Sharayu Jangam
    • , Cenying Liu
    • , Hailun Ni
    • , Marjolein H. Willemsen
    • , Bregje W. van Bon
    • , Tuula Rinne
    • , Servi J. C. Stevens
    • , Tjitske Kleefstra
    • , Han G. Brunner
    • , Helger G. Yntema
    • , Min Long
    • , Wenjing Zhao
    • , Zhengmao Hu
    • , Cindy Colson
    • , Nicolas Richard
    • , Charles E. Schwartz
    • , Corrado Romano
    • , Lucia Castiglia
    • , Maria Bottitta
    • , Shweta U. Dhar
    • , Deanna J. Erwin
    • , Lisa Emrick
    • , Boris Keren
    • , Alexandra Afenjar
    • , Baosheng Zhu
    • , Bing Bai
    • , Pawel Stankiewicz
    • , Kristin Herman
    • , Deborah A. Nickerson
    • , Michael J. Bamshad
    • , Saadet Mercimek-Andrews
    • , Jane Juusola
    • , Amy B. Wilfert
    • , Rami Abou Jamra
    • , Benjamin Büttner
    • , Heather C. Mefford
    • , Alison M. Muir
    • , Ingrid E. Scheffer
    • , Brigid M. Regan
    • , Stephen Malone
    • , Jozef Gecz
    • , Jan Cobben
    • , Marjan M. Weiss
    • , Quinten Waisfisz
    • , Emilia K. Bijlsma
    • , Mariëtte J. V. Hoffer
    • , Claudia A. L. Ruivenkamp
    • , Stefano Sartori
    • , Fan Xia
    • , Jill A. Rosenfeld
    • , Raphael A. Bernier
    • , Michael F. Wangler
    • , Shinya Yamamoto
    • , Kun Xia
    • , Alexander P. A. Stegmann
    • , Hugo J. Bellen
    • , Alessandra Murgia
    •  & Evan E. Eichler
  • Article
    | Open Access

    Retrotransposition events have been linked to some human disorders. Here, Gardner et al. systematically search for mobile genetic elements (ME) in trio whole exome-sequencing datasets and ascertain 9 de novo MEs and further estimate genome-wide germline ME burden and constraint.

    • Eugene J. Gardner
    • , Elena Prigmore
    • , Giuseppe Gallone
    • , Petr Danecek
    • , Kaitlin E. Samocha
    • , Juliet Handsaker
    • , Sebastian S. Gerety
    • , Holly Ironfield
    • , Patrick J. Short
    • , Alejandro Sifrim
    • , Tarjinder Singh
    • , Kate E. Chandler
    • , Emma Clement
    • , Katherine L. Lachlan
    • , Katrina Prescott
    • , Elisabeth Rosser
    • , David R. FitzPatrick
    • , Helen V. Firth
    •  & Matthew E. Hurles
  • Article
    | Open Access

    How do diversity (entropy) and integration of activity across brain regions interact to support consciousness? Here the authors show that anaesthetised individuals and patients with disorders of consciousness exhibit overlapping reductions in both diversity and integration in the brain’s default mode network.

    • Andrea I. Luppi
    • , Michael M. Craig
    • , Ioannis Pappas
    • , Paola Finoia
    • , Guy B. Williams
    • , Judith Allanson
    • , John D. Pickard
    • , Adrian M. Owen
    • , Lorina Naci
    • , David K. Menon
    •  & Emmanuel A. Stamatakis
  • Article
    | Open Access

    Dystrophin-deficient mice are used to test corrective strategies for Duchenne muscular dystrophy, but evaluation of dystrophin expression requires collection of tissue samples from specific muscles and time points. Here, the authors generate mice in which dystrophin expression is coupled to luciferase, and show that bioluminescence allows non-invasive monitoring of dystrophin expression following genome editing.

    • Leonela Amoasii
    • , Hui Li
    • , Yu Zhang
    • , Yi-Li Min
    • , Efrain Sanchez-Ortiz
    • , John M. Shelton
    • , Chengzu Long
    • , Alex A. Mireault
    • , Samadrita Bhattacharyya
    • , John R. McAnally
    • , Rhonda Bassel-Duby
    •  & Eric N. Olson
  • Article
    | Open Access

    A recent GWAS reported 12 genetic loci for attention deficit/hyperactivity disorder (ADHD). Here, Liao et al. perform transcriptomic imputation using these data and 12 brain-relevant tissues from GTEx and CMC to identify 9 genes associated with ADHD by TWAS, 3 of which had not yet been reported for ADHD.

    • Calwing Liao
    • , Alexandre D. Laporte
    • , Dan Spiegelman
    • , Fulya Akçimen
    • , Ridha Joober
    • , Patrick A. Dion
    •  & Guy A. Rouleau
  • Article
    | Open Access

    ABCC9 encodes the SUR2 subunit of KATP channels and dominant genetic variants in ABCC9 have been associated with cardiac phenotypes. Here, the authors report recessive ABCC9 mutations in individuals with mild intellectual disability, myopathy and cardiac systolic dysfunction which is associated with loss of KATP channel function.

    • Marie F. Smeland
    • , Conor McClenaghan
    • , Helen I. Roessler
    • , Sanne Savelberg
    • , Geir Åsmund Myge Hansen
    • , Helene Hjellnes
    • , Kjell Arne Arntzen
    • , Kai Ivar Müller
    • , Andreas Rosenberger Dybesland
    • , Theresa Harter
    • , Monica Sala-Rabanal
    • , Chris H. Emfinger
    • , Yan Huang
    • , Soma S. Singareddy
    • , Jamie Gunn
    • , David F. Wozniak
    • , Attila Kovacs
    • , Maarten Massink
    • , Federico Tessadori
    • , Sarah M. Kamel
    • , Jeroen Bakkers
    • , Maria S. Remedi
    • , Marijke Van Ghelue
    • , Colin G. Nichols
    •  & Gijs van Haaften
  • Article
    | Open Access

    Accumulation of abnormal tau protein drives neurodegeneration in Alzheimer’s disease and related dementia disorders. Here, the authors demonstrate the endoplasmic reticulum unfolded protein response mediator XBP-1 controls pathological tau accumulation and the resultant neurodegeneration in a transgenic C. elegans model.

    • Sarah M. Waldherr
    • , Timothy J. Strovas
    • , Taylor A. Vadset
    • , Nicole F. Liachko
    •  & Brian C. Kraemer
  • Article
    | Open Access

    MR-focused ultrasound can be used to transiently open the blood-brain barrier (BBB). Here, the authors report the results of a first-in-human trial on four patients with amyotrophic lateral sclerosis (ALS), showing that the procedure reversibly permeabilised the BBB in the motor cortex without complications, and suggest that the procedure could in the future be used to increase drug delivery in ALS patients.

    • Agessandro Abrahao
    • , Ying Meng
    • , Maheleth Llinas
    • , Yuexi Huang
    • , Clement Hamani
    • , Todd Mainprize
    • , Isabelle Aubert
    • , Chinthaka Heyn
    • , Sandra E. Black
    • , Kullervo Hynynen
    • , Nir Lipsman
    •  & Lorne Zinman
  • Article
    | Open Access

    Matching iPSC donors’ and patients’ HLA haplotypes has been proposed as a way to generate cell therapy products with enhanced immunological compatibility. Here the authors show that MHC matching alone is insufficient to grant long-term survival of neuronal grafts in the lesioned brain of non-human primates.

    • Romina Aron Badin
    • , Aurore Bugi
    • , Susannah Williams
    • , Marta Vadori
    • , Marie Michael
    • , Caroline Jan
    • , Alberto Nassi
    • , Sophie Lecourtois
    • , Antoine Blancher
    • , Emanuele Cozzi
    • , Philippe Hantraye
    •  & Anselme L. Perrier
  • Article
    | Open Access

    Spinal and bulbar muscular atrophy is a neuromuscular disease caused by an expanded CAG repeat in the androgen receptor gene. Here the authors show that Src kinase signaling is activated in a mouse model of the disease, and that Src inhibition improves pathology and behavioral symptoms in mice.

    • Madoka Iida
    • , Kentaro Sahashi
    • , Naohide Kondo
    • , Hideaki Nakatsuji
    • , Genki Tohnai
    • , Yutaka Tsutsumi
    • , Seiya Noda
    • , Ayuka Murakami
    • , Kazunari Onodera
    • , Yohei Okada
    • , Masahiro Nakatochi
    • , Yuka Tsukagoshi Okabe
    • , Shinobu Shimizu
    • , Masaaki Mizuno
    • , Hiroaki Adachi
    • , Hideyuki Okano
    • , Gen Sobue
    •  & Masahisa Katsuno
  • Article
    | Open Access

    The precise mechanisms that lead to medication-overuse headaches (MOH), which can occur with both over-the-counter and prescription pain-relief medicines, are still uncertain. In this study, authors show that the abnormal activation of dural nociceptor Nav1.9 channels by Nitric Oxide is responsible for triptan-induced MOH, causing hyperexcitability of dural nociceptors and headache.

    • Caroline Bonnet
    • , Jizhe Hao
    • , Nancy Osorio
    • , Anne Donnet
    • , Virginie Penalba
    • , Jérôme Ruel
    •  & Patrick Delmas
  • Article
    | Open Access

    The use of PET for detection of Aβ in the brain in AD has limitations; studies also indicate that retinal changes, including Aβ deposition, occur in AD. Here the authors demonstrate the potential to use in vivo retinal hyperspectral imaging as a surrogate for brain accumulation of Aβ.

    • Xavier Hadoux
    • , Flora Hui
    • , Jeremiah K. H. Lim
    • , Colin L. Masters
    • , Alice Pébay
    • , Sophie Chevalier
    • , Jason Ha
    • , Samantha Loi
    • , Christopher J. Fowler
    • , Christopher Rowe
    • , Victor L. Villemagne
    • , Edward N. Taylor
    • , Christopher Fluke
    • , Jean-Paul Soucy
    • , Frédéric Lesage
    • , Jean-Philippe Sylvestre
    • , Pedro Rosa-Neto
    • , Sulantha Mathotaarachchi
    • , Serge Gauthier
    • , Ziad S. Nasreddine
    • , Jean Daniel Arbour
    • , Marc-André Rhéaume
    • , Sylvain Beaulieu
    • , Mohamed Dirani
    • , Christine T. O. Nguyen
    • , Bang V. Bui
    • , Robert Williamson
    • , Jonathan G. Crowston
    •  & Peter van Wijngaarden
  • Article
    | Open Access

    Brain oscillations may be disrupted in children with autism spectrum disorder. The authors performed a longitudinal study of electroencephalography recordings and found that EEG recordings from the first year after birth can distinguish healthy children from children with autism spectrum disorder.

    • Laurel J. Gabard-Durnam
    • , Carol Wilkinson
    • , Kush Kapur
    • , Helen Tager-Flusberg
    • , April R. Levin
    •  & Charles A. Nelson
  • Article
    | Open Access

    TDP43 aggregates are a hallmark of amyotrophic lateral sclerosis. By using deep mutagenesis to measure the toxicity of more than 50,000 mutations in the prion domain of TDP43, the authors conclude that mutations that increase toxicity promote formation of liquid-like condensates, while aggregation of TDP43 is protective for the cell.

    • Benedetta Bolognesi
    • , Andre J. Faure
    • , Mireia Seuma
    • , Jörn M. Schmiedel
    • , Gian Gaetano Tartaglia
    •  & Ben Lehner
  • Article
    | Open Access

    While energy metabolism has been repeatedly linked to ALS, motor neuron metabolism remains poorly studied. Here, authors show that human iPSCs rewire specific metabolic routes when they differentiate into functional motor neurons and that ALS-causing mutations in FUS do not affect energy metabolism.

    • Tijs Vandoorne
    • , Koen Veys
    • , Wenting Guo
    • , Adria Sicart
    • , Katlijn Vints
    • , Ann Swijsen
    • , Matthieu Moisse
    • , Guy Eelen
    • , Natalia V. Gounko
    • , Laura Fumagalli
    • , Raheem Fazal
    • , Christine Germeys
    • , Annelies Quaegebeur
    • , Sarah-Maria Fendt
    • , Peter Carmeliet
    • , Catherine Verfaillie
    • , Philip Van Damme
    • , Bart Ghesquière
    • , Katrien De Bock
    •  & Ludo Van Den Bosch
  • Article
    | Open Access

    CDK5 is known to drive glioblastoma tumorigenicity but the downstream molecular mechanism is unknown. Here, the authors show that CDK5 activates STAT3 signalling via the nuclear import of TRIM59, which leads to the degradation of the tumour suppressor macroH2A1.

    • Youzhou Sang
    • , Yanxin Li
    • , Yingwen Zhang
    • , Angel A. Alvarez
    • , Bo Yu
    • , Weiwei Zhang
    • , Bo Hu
    • , Shi-Yuan Cheng
    •  & Haizhong Feng
  • Article
    | Open Access

    The molecular mechanisms driving proliferation in the pediatric brain cancer epdendymoma are poorly understood. Here the authors show that a YAP1- MAMLD1 fusion drives tumor formation in mice and show that the fusion protein can collaborate with the TEAD and NFI transcription factors.

    • Kristian W. Pajtler
    • , Yiju Wei
    • , Konstantin Okonechnikov
    • , Patricia B. G. Silva
    • , Mikaella Vouri
    • , Lei Zhang
    • , Sebastian Brabetz
    • , Laura Sieber
    • , Melissa Gulley
    • , Monika Mauermann
    • , Tatjana Wedig
    • , Norman Mack
    • , Yuka Imamura Kawasawa
    • , Tanvi Sharma
    • , Marc Zuckermann
    • , Felipe Andreiuolo
    • , Eric Holland
    • , Kendra Maass
    • , Huiqin Körkel-Qu
    • , Hai-Kun Liu
    • , Felix Sahm
    • , David Capper
    • , Jens Bunt
    • , Linda J. Richards
    • , David T. W. Jones
    • , Andrey Korshunov
    • , Lukas Chavez
    • , Peter Lichter
    • , Mikio Hoshino
    • , Stefan M. Pfister
    • , Marcel Kool
    • , Wei Li
    •  & Daisuke Kawauchi
  • Article
    | Open Access

    Resolvins are endogenous lipids with pro-resolving activity. Here the authors find that rats overexpressing human α-synuclein show defects in dopamine signalling before dopamine cell loss, and that this is associated with low Resolvin D1 levels and neuroinflammation.

    • Paraskevi Krashia
    • , Alberto Cordella
    • , Annalisa Nobili
    • , Livia La Barbera
    • , Mauro Federici
    • , Alessandro Leuti
    • , Federica Campanelli
    • , Giuseppina Natale
    • , Gioia Marino
    • , Valeria Calabrese
    • , Francescangelo Vedele
    • , Veronica Ghiglieri
    • , Barbara Picconi
    • , Giulia Di Lazzaro
    • , Tommaso Schirinzi
    • , Giulia Sancesario
    • , Nicolas Casadei
    • , Olaf Riess
    • , Sergio Bernardini
    • , Antonio Pisani
    • , Paolo Calabresi
    • , Maria Teresa Viscomi
    • , Charles Nicholas Serhan
    • , Valerio Chiurchiù
    • , Marcello D’Amelio
    •  & Nicola Biagio Mercuri
  • Article
    | Open Access

    Dysregulation of intracellular calcium is reported in Alzheimer’s disease. Here the authors show that loss of the mitochondrial Na+ /Ca2+ exchanger, NCLX – primary route of mitochondrial calcium efflux, precedes neuronal pathology in experimental models and contributes to Alzheimer’s disease progression.

    • Pooja Jadiya
    • , Devin W. Kolmetzky
    • , Dhanendra Tomar
    • , Antonio Di Meco
    • , Alyssa A. Lombardi
    • , Jonathan P. Lambert
    • , Timothy S. Luongo
    • , Marthe H. Ludtmann
    • , Domenico Praticò
    •  & John W. Elrod
  • Article
    | Open Access

    In multiple sclerosis (MS), antigen-presenting cells inducing cytotoxic T cell response against mature oligodendrocytes remain to be identified. Here the authors show that oligodendrocyte precursors cross-present antigen taken up from mature oligodendrocytes, and are targeted by cytotoxic T cells in cell culture and in an animal model of MS.

    • Leslie Kirby
    • , Jing Jin
    • , Jaime Gonzalez Cardona
    • , Matthew D. Smith
    • , Kyle A. Martin
    • , Jingya Wang
    • , Hayley Strasburger
    • , Leyla Herbst
    • , Maya Alexis
    • , Jodi Karnell
    • , Todd Davidson
    • , Ranjan Dutta
    • , Joan Goverman
    • , Dwight Bergles
    •  & Peter A. Calabresi
  • Article
    | Open Access

    Glioma therapy with checkpoint inhibitors has limited blood–brain barrier (BBB) penetration and therapeutic effects. Here, the authors develop nanopolymer-conjugated checkpoint inhibitors and show their trans-BBB delivery and anti-glioma efficacy.

    • Anna Galstyan
    • , Janet L. Markman
    • , Ekaterina S. Shatalova
    • , Antonella Chiechi
    • , Alan J. Korman
    • , Rameshwar Patil
    • , Dmytro Klymyshyn
    • , Warren G. Tourtellotte
    • , Liron L. Israel
    • , Oliver Braubach
    • , Vladimir A. Ljubimov
    • , Leila A. Mashouf
    • , Arshia Ramesh
    • , Zachary B. Grodzinski
    • , Manuel L. Penichet
    • , Keith L. Black
    • , Eggehard Holler
    • , Tao Sun
    • , Hui Ding
    • , Alexander V. Ljubimov
    •  & Julia Y. Ljubimova
  • Article
    | Open Access

    Although defects in nucleocytoplasmic transport (NCT) may be central to the pathogenesis of ALS, the molecular mechanisms modulating the nuclear pore function are still largely unknown. Here, authors show that genetic and pharmacological modulation of actin polymerization disrupts nuclear pore integrity and can be targeted to rescue nuclear pore instability and dysfunction caused by mutant PFN1 as well as by C9ORF72 repeat expansion

    • Anthony Giampetruzzi
    • , Eric W. Danielson
    • , Valentina Gumina
    • , Maryangel Jeon
    • , Sivakumar Boopathy
    • , Robert H. Brown
    • , Antonia Ratti
    • , John E. Landers
    •  & Claudia Fallini
  • Article
    | Open Access

    The adaptor protein p11 and K+ channel TASK1 have overlapping distributions in the CNS. Here, the authors demonstrate that the transcription factor Sp1 regulates p11 levels, which in turn affects intrinsic membrane properties and can contribute to degeneration of motor neurons in disease and injury models.

    • Victoria García-Morales
    • , Guillermo Rodríguez-Bey
    • , Laura Gómez-Pérez
    • , Germán Domínguez-Vías
    • , David González-Forero
    • , Federico Portillo
    • , Antonio Campos-Caro
    • , Ángela Gento-Caro
    • , Noura Issaoui
    • , Rosa M. Soler
    • , Ana Garcera
    •  & Bernardo Moreno-López
  • Article
    | Open Access

    Treating Alzheimer’s disease, one of the most common neurodegenerative diseases, is of wide interest. Here, the authors report on the development of casein coated gold nanoparticles which were able to cross the blood brain barrier and protect against amyloid beta toxicity in a zebrafish model.

    • Ibrahim Javed
    • , Guotao Peng
    • , Yanting Xing
    • , Tianyu Yu
    • , Mei Zhao
    • , Aleksandr Kakinen
    • , Ava Faridi
    • , Clare L. Parish
    • , Feng Ding
    • , Thomas P. Davis
    • , Pu Chun Ke
    •  & Sijie Lin
  • Article
    | Open Access

    Mutations in the Protein Phosphatase PPM1D are oncogenic in certain cancers including diffuse intrinsic pontine glioma (DIPG). Here, the authors show that PPM1D mutations in DIPG induce the silencing of the nicotinic acid phosphoribosyltransferase gene and display synthetic lethality with nicotinamide phosphoribosyltransferase inhibitors.

    • Nathan R. Fons
    • , Ranjini K. Sundaram
    • , Gregory A. Breuer
    • , Sen Peng
    • , Ryan L. McLean
    • , Aravind N. Kalathil
    • , Mark S. Schmidt
    • , Diana M. Carvalho
    • , Alan Mackay
    • , Chris Jones
    • , Ángel M. Carcaboso
    • , Javad Nazarian
    • , Michael E. Berens
    • , Charles Brenner
    •  & Ranjit S. Bindra
  • Article
    | Open Access

    Genetics implicate microglia in Alzheimer’s disease pathogenesis, but their roles remain unclear. Here, the authors find that microglial depletion in a mouse model of Alzheimer’s disease impairs plaque formation and that Aβ-induced changes in neuronal gene expression are microglia-mediated.

    • Elizabeth Spangenberg
    • , Paul L. Severson
    • , Lindsay A. Hohsfield
    • , Joshua Crapser
    • , Jiazhong Zhang
    • , Elizabeth A. Burton
    • , Ying Zhang
    • , Wayne Spevak
    • , Jack Lin
    • , Nicole Y. Phan
    • , Gaston Habets
    • , Andrey Rymar
    • , Garson Tsang
    • , Jason Walters
    • , Marika Nespi
    • , Parmveer Singh
    • , Stephanie Broome
    • , Prabha Ibrahim
    • , Chao Zhang
    • , Gideon Bollag
    • , Brian L. West
    •  & Kim N. Green
  • Article
    | Open Access

    Pilocytic astrocytoma is a low-grade pediatric glioma, characterized by a single BRAF rearrangement. Here, Reitman and colleagues use single-cell RNA sequencing to reveal molecular hallmarks of the disease that might be targeted therapeutically.

    • Zachary J. Reitman
    • , Brenton R. Paolella
    • , Guillaume Bergthold
    • , Kristine Pelton
    • , Sarah Becker
    • , Robert Jones
    • , Claire E. Sinai
    • , Hayley Malkin
    • , Ying Huang
    • , Leslie Grimmet
    • , Zachary T. Herbert
    • , Yu Sun
    • , Jessica L. Weatherbee
    • , John A. Alberta
    • , John F. Daley
    • , Orit Rozenblatt-Rosen
    • , Alexandra L. Condurat
    • , Kenin Qian
    • , Prasidda Khadka
    • , Rosalind A. Segal
    • , Daphne Haas-Kogan
    • , Mariella G. Filbin
    • , Mario L. Suva
    • , Aviv Regev
    • , Charles D. Stiles
    • , Mark W. Kieran
    • , Liliana Goumnerova
    • , Keith L. Ligon
    • , Alex K. Shalek
    • , Pratiti Bandopadhayay
    •  & Rameen Beroukhim
  • Article
    | Open Access

    A main symptom of chronic insufficient sleep is excessive daytime sleepiness. Here, Wang et al. report 42 genome-wide significant loci for self-reported daytime sleepiness in 452,071 individuals from the UK Biobank that cluster into two biological subtypes of either sleep propensity or sleep fragmentation.

    • Heming Wang
    • , Jacqueline M. Lane
    • , Samuel E. Jones
    • , Hassan S. Dashti
    • , Hanna M. Ollila
    • , Andrew R. Wood
    • , Vincent T. van Hees
    • , Ben Brumpton
    • , Bendik S. Winsvold
    • , Katri Kantojärvi
    • , Teemu Palviainen
    • , Brian E. Cade
    • , Tamar Sofer
    • , Yanwei Song
    • , Krunal Patel
    • , Simon G. Anderson
    • , David A. Bechtold
    • , Jack Bowden
    • , Richard Emsley
    • , Simon D. Kyle
    • , Max A. Little
    • , Andrew S. Loudon
    • , Frank A. J. L. Scheer
    • , Shaun M. Purcell
    • , Rebecca C. Richmond
    • , Kai Spiegelhalder
    • , Jessica Tyrrell
    • , Xiaofeng Zhu
    • , Christer Hublin
    • , Jaakko A. Kaprio
    • , Kati Kristiansson
    • , Sonja Sulkava
    • , Tiina Paunio
    • , Kristian Hveem
    • , Jonas B. Nielsen
    • , Cristen J. Willer
    • , John-Anker Zwart
    • , Linn B. Strand
    • , Timothy M. Frayling
    • , David Ray
    • , Deborah A. Lawlor
    • , Martin K. Rutter
    • , Michael N. Weedon
    • , Susan Redline
    •  & Richa Saxena
  • Article
    | Open Access

    STAT3 activates distinct transcriptional programmes within cancer cells. In this study, the authors find that, in glioma, a STAT3-mediated expression signature can stratify patients for targeted precision therapy.

    • Melanie Si Yan Tan
    • , Edwin Sandanaraj
    • , Yuk Kien Chong
    • , See Wee Lim
    • , Lynnette Wei Hsien Koh
    • , Wai Hoe Ng
    • , Nguan Soon Tan
    • , Patrick Tan
    • , Beng Ti Ang
    •  & Carol Tang
  • Article
    | Open Access

    Hsp chaperones stabilize the inactive conformation of androgen receptor (AR) and are released upon hormone-induced AR activation. Here, the authors locate the Hsp binding region on AR, and show that Hsp70 reduces AR aggregation and promotes AR degradation in cellular and mouse models of a neuromuscular disorder.

    • Bahareh Eftekharzadeh
    • , Varuna C. Banduseela
    • , Giulio Chiesa
    • , Paula Martínez-Cristóbal
    • , Jennifer N. Rauch
    • , Samir R. Nath
    • , Daniel M. C. Schwarz
    • , Hao Shao
    • , Marta Marin-Argany
    • , Claudio Di Sanza
    • , Elisa Giorgetti
    • , Zhigang Yu
    • , Roberta Pierattelli
    • , Isabella C. Felli
    • , Isabelle Brun-Heath
    • , Jesús García
    • , Ángel R. Nebreda
    • , Jason E. Gestwicki
    • , Andrew P. Lieberman
    •  & Xavier Salvatella