Featured
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Structural insights into vesicular monoamine storage and drug interactions
Monoamines and neurotoxicants share a binding pocket in VMAT1 featuring polar sites for specificity and a wrist-and-fist shape for versatility, and monoamine enrichment in storage vesicles arises from dominant import via favoured lumenal-open transition of VMAT1 and protonation-precluded binding during its cytoplasmic-open transition.
- Jin Ye
- , Huaping Chen
- & Weikai Li
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Research Briefing |
Dysregulated cellular stress management becomes a source of stress
Stress responses protect cells from harmful conditions, but once the stress has resolved, these responses must be actively turned off to avoid cell damage that might lead to the development of neurodegenerative disease.
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News & Views |
Non-neuronal brain cells modulate behaviour
A single gene in astrocytes can constrain repetitive behaviours, indicating that these cells are regulators of behavioural disruption in conditions such as Huntington’s disease and obsessive–compulsive disorder.
- Anna Kruyer
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News & Views |
Synchronized neuronal activity drives waste fluid flow
Active neurons can stimulate the clearance of their own metabolic waste by driving changes to ion gradients in the surrounding fluid and by promoting the pulsation of nearby blood vessels.
- Lauren Hablitz
- & Maiken Nedergaard
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Article
| Open Access
A model of human neural networks reveals NPTX2 pathology in ALS and FTLD
A neural stem cell culture system derived from induced pluripotent stem cells forms a network of synaptically connected and electrophysiologically active neurons that were used as a model system to identify a mechanism of TDP-43-induced neurodegeneration.
- Marian Hruska-Plochan
- , Vera I. Wiersma
- & Magdalini Polymenidou
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News |
Early dementia diagnosis: blood proteins reveal at-risk people
The results of a large-scale screening study could be used to develop blood tests to diagnose diseases such as Alzheimer’s before symptoms take hold.
- Miryam Naddaf
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News |
Signs of ‘transmissible’ Alzheimer’s seen in people who received growth hormone
The findings support a controversial hypothesis that proteins related to the neurodegenerative disease can be ‘seeded’ in the brain through material taken from cadavers.
- Carissa Wong
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News |
Obesity drugs have another superpower: taming inflammation
The blockbuster medications that reduce body weight also reduce inflammation in organs such as the brain, raising hopes that they can treat Parkinson's and Alzheimer's diseases.
- Mariana Lenharo
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News |
Ancient DNA reveals origins of multiple sclerosis in Europe
A huge cache of ancient genomes spanning tens of thousands of years reveals the roots of traits in modern Europeans.
- Sara Reardon
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News |
Potent psychedelic drug banishes PTSD, small study finds
Military veterans with cognitive and psychological problems saw drastic improvements after a dose of ibogaine.
- Max Kozlov
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Article
| Open Access
m1A in CAG repeat RNA binds to TDP-43 and induces neurodegeneration
TDP-43 binds to N1-methyladenosine on CAG repeat RNA, resulting in the formation of gel-like TDP-43 aggregates in the cytoplasm that resemble those observed in neurological disease pathology.
- Yuxiang Sun
- , Hui Dai
- & Yinsheng Wang
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News |
Spinal implant helps man with advanced Parkinson’s to walk without falling
Electrical stimulation improved his mobility, although researchers say that a larger study is needed to assess the device.
- Emily Waltz
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News |
The brain cells linked to protection against dementia
People with an abundance of specific neurons are more likely to escape cognitive decline despite having signs of Alzheimer’s in their brains.
- Sara Reardon
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Article |
A high-performance neuroprosthesis for speech decoding and avatar control
A study using high-density surface recordings of the speech cortex in a person with limb and vocal paralysis demonstrates real-time decoding of brain activity into text, speech sounds and orofacial movements.
- Sean L. Metzger
- , Kaylo T. Littlejohn
- & Edward F. Chang
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News & Views |
How the cGAS–STING system links inflammation and cognitive decline
When DNA is misplaced inside cells, the cGAS–STING molecular system triggers inflammation. It emerges that stimulation of this mechanism in microglial cells of the brain during ageing contributes to cognitive decline.
- Bart J. L. Eggen
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News |
Alzheimer’s drug donanemab helps most when taken at earliest disease stage, study finds
But the drug, an antibody that attacks the protein amyloid, does not work as well in people with more advanced disease.
- Sara Reardon
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Article
| Open Access
A framework for individualized splice-switching oligonucleotide therapy
Whole-genome sequencing analyses in a cohort of individuals with ataxia-telangiectasia are used to identify genetic variants that might be amenable to treatment with splice-switching antisense oligonucleotides (ASOs), and develop ASOs with therapeutic potential.
- Jinkuk Kim
- , Sijae Woo
- & Timothy W. Yu
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News |
Anti-ageing protein injection boosts monkeys’ memories
First primate studies to show cognitive benefits of the protein klotho could be a step towards clinical applications.
- Lilly Tozer
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Article |
Locus for severity implicates CNS resilience in progression of multiple sclerosis
A genome-wide association study including 22,389 cases of multiple sclerosis finds an association with disease progression at the DYSF–ZNF638 and DNM3–PIGC loci and identifies a potential of higher educational attainment in slowing disease progression.
- Adil Harroud
- , Pernilla Stridh
- & Kári Stefánsson
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News |
Does shingles vaccination cut dementia risk? Large study hints at a link
Analysis of nearly 300,000 people finds an association between the shingles jab and a lower rate of dementia — but questions linger.
- Sara Reardon
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Article
| Open Access
Walking naturally after spinal cord injury using a brain–spine interface
A reliable digital bridge restored communication between the brain and spinal cord and enabled natural walking in a participant with spinal cord injury.
- Henri Lorach
- , Andrea Galvez
- & Grégoire Courtine
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Article
| Open Access
Heteromeric clusters of ubiquitinated ER-shaping proteins drive ER-phagy
The membrane-shaping protein ARL6IP1 is involved in the selective degradation of the endoplasmic reticulum, and this process depends on its ubiquitination and interaction with other membrane-shaping proteins such as FAM134B.
- Hector Foronda
- , Yangxue Fu
- & Christian A. Hübner
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Technology Feature |
Brain imaging: fMRI advances make scans sharper and faster
Researchers are finding ways to improve one of neuroscientists’ favourite tools: functional magnetic resonance imaging.
- Diana Kwon
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News & Views |
Activated immune cells drive neurodegeneration in an Alzheimer’s model
An analysis of mice carrying the protein tau — a hallmark of Alzheimer’s disease — reveals that immune cells collaborate to drive tau-mediated neurodegeneration, and that drugs already in use in the clinic can combat this decline.
- Ian H. Guldner
- & Tony Wyss-Coray
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News & Views |
Drug trial for Alzheimer’s disease is a game changer
An antibody treatment reduces measurements of brain abnormalities called amyloid plaques in people with Alzheimer’s disease, and lessens clinical decline. This result will help in developing therapies to treat and prevent the disease.
- Eric M. Reiman
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News & Views |
The Alzheimer’s risk gene APOE modulates the gut–brain axis
Signals from gut microorganisms to the brain might be involved in neurodegeneration. It emerges that the gene APOE — variants of which each confer a different risk of Alzheimer’s disease — has a role in modulating this gut–brain communication.
- Alfonso Martín-Peña
- & Malú Gámez Tansey
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Research Highlight |
Link between brain atrophy and the microbiome emerges in mice
Changes similar to those seen in Alzheimer’s disease are less pronounced in mice with minimal levels of gut bacteria.
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Article |
Autonomous rhythmic activity in glioma networks drives brain tumour growth
A population of highly interconnected cells in glioblastoma makes these tumours resistant to general damage but vulnerable to targeted disruption of this small fraction of cells and their rhythmic Ca2+ oscillations.
- David Hausmann
- , Dirk C. Hoffmann
- & Frank Winkler
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Article
| Open Access
Medin co-aggregates with vascular amyloid-β in Alzheimer’s disease
Medin promotes the formation of vascular aggregates with amyloid-β in mouse models and in human patients with Alzheimer’s disease, and is associated with vascular defects and cognitive decline.
- Jessica Wagner
- , Karoline Degenhardt
- & Jonas J. Neher
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Article
| Open Access
Stroke genetics informs drug discovery and risk prediction across ancestries
A cross-ancestry meta-analysis of genome-wide association studies identifies association signals for stroke and its subtypes at 89 (61 new) independent loci, reveals putative causal genes, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as potential drug targets, and provides cross-ancestry integrative risk prediction.
- Aniket Mishra
- , Rainer Malik
- & Stephanie Debette
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Article |
A mechanism for oxidative damage repair at gene regulatory elements
The nuclear mitotic apparatus protein NuMA helps to protect genes from oxidative damage by occupying regions around transcription start sites, binding DNA repair factors and promoting transcription following damage.
- Swagat Ray
- , Arwa A. Abugable
- & Sherif F. El-Khamisy
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Research Briefing |
Tracing the brain circuitry underlying movement and mood symptoms in Parkinson’s disease
Parkinson’s disease causes slowness of movement, tremor and stiffness, along with mood symptoms such as depression. The brain’s parafascicular thalamus is shown to contain distinct neural circuits for locomotion, motor learning and depression-like states, and targeting these circuits alleviates some deficits in a mouse model of the disease.
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News |
Young brain fluid improves memory in old mice
A protein in cerebrospinal fluid helps boost cells that maintain brain function.
- Jude Coleman
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Article |
Somatic genomic changes in single Alzheimer’s disease neurons
Analyses of single-cell whole-genome sequencing data show that somatic mutations are increased in the brain of individuals with Alzheimer’s disease compared to neurotypical individuals, with a pattern of genomic damage distinct from that of normal ageing.
- Michael B. Miller
- , August Yue Huang
- & Christopher A. Walsh
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News & Views |
An unexpected protein aggregate in diseased and ageing brains
Protein fibrils accumulate in the brain during neurodegeneration. Cryo-electron microscopy has now uncovered fibrils of a protein not previously thought to accumulate.
- Hideyuki Takahashi
- & Stephen M. Strittmatter
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Article |
Amyloid fibrils in FTLD-TDP are composed of TMEM106B and not TDP-43
Amyloid fibrils extracted from brains of patients with frontotemporal lobar degeneration with TAR DNA-binding-protein immunoreactivity (FTLD-TDP) are made up of transmembrane protein 106B.
- Yi Xiao Jiang
- , Qin Cao
- & David S. Eisenberg
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News Feature |
Could drugs prevent Alzheimer’s? These trials aim to find out
Researchers are giving drugs to healthy people in hope of clearing away toxic proteins in the brain and warding off neurodegeneration.
- Alison Abbott
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News & Views |
Mechanism underlying a risk gene in neurodegeneration
Messenger RNA from the gene UNC13A is misprocessed in people who have neurodegenerative diseases known as ALS and FTD. The discovery could explain the disease risk associated with variants in this gene.
- Noa Lipstein
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Article |
Clonally expanded B cells in multiple sclerosis bind EBV EBNA1 and GlialCAM
The identification of high-affinity molecular mimicry between the Epstein–Barr virus (EBV) transcription factor EBNA1 and the CNS protein GlialCAM provides a mechanistic link between multiple sclerosis and EBV.
- Tobias V. Lanz
- , R. Camille Brewer
- & William H. Robinson
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News & Views |
Aggregates of TDP-43 protein spiral into view
In some neurodegenerative diseases, a protein called TDP-43 forms aggregates in the brain, resulting in neuronal cell death. The structure of these aggregates and their properties have been unveiled.
- Hana M. Odeh
- & James Shorter
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Article |
Structures of the σ2 receptor enable docking for bioactive ligand discovery
Crystal structures of the σ2 receptor are determined and used to perform a docking screen of nearly 500 million molecules, identifying σ2-selective ligands and providing insight into the role of σ2 in neuropathic pain.
- Assaf Alon
- , Jiankun Lyu
- & Andrew C. Kruse
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News Explainer |
More Alzheimer’s drugs head for FDA review: what scientists are watching
Eli Lilly and other pharma firms have begun submitting their anti-amyloid drug hopefuls for approval. But questions linger over the controversial precedent set by Biogen’s aducanumab.
- Asher Mullard
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News & Views |
Mice with disrupted mitochondria used to model Parkinson’s disease
Mice in which organelles called mitochondria are disrupted in vulnerable neuronal cells provide a new model of Parkinson’s disease. The pattern of neurodegeneration challenges long-held ideas about the disease’s motor symptoms.
- Zak Doric
- & Ken Nakamura
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Article |
Disruption of mitochondrial complex I induces progressive parkinsonism
Dysfunction of mitochondrial complex I in mice is sufficient to cause progressive parkinsonism in which the loss of nigral dopamine release critically contributes to motor dysfunction.
- Patricia González-Rodríguez
- , Enrico Zampese
- & D. James Surmeier
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News & Views |
Structural strains of misfolded tau protein define different diseases
In diseases called tauopathies, misfolded tau proteins form aggregates called fibrils. Fibrils from nine different tauopathies show that tau misfolds in many ways, enabling the diseases to be classified according to fibril structure.
- Henning Stahlberg
- & Roland Riek
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Article |
Kainate receptor modulation by NETO2
The authors report the structures of glutamate-gated kainate receptors in complex with NETO2 in both the resting and the desensitized states and reveal how kainate receptors in the brain are regulated by NETO2.
- Lingli He
- , Jiahui Sun
- & Yan Zhao
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Article |
A lymphocyte–microglia–astrocyte axis in chronic active multiple sclerosis
Single-nucleus transcriptomics defines a diverse set of immune and glial cells at the chronically inflamed leading edge of demyelinated white matter lesions in patients with multiple sclerosis.
- Martina Absinta
- , Dragan Maric
- & Daniel S. Reich
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Article |
DAXX represents a new type of protein-folding enabler
A protein chaperone system is identified that consists of proteins with poly-Asp/Glu sequence, and may have an important role in diseases characterized by protein aggregation.
- Liangqian Huang
- , Trisha Agrawal
- & Xiaolu Yang
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News & Views |
A protective signal between the brain’s supporting cells in Alzheimer’s disease
In a mouse model of Alzheimer’s disease, interleukin-3 protein released by cells called astrocytes activates microglia, the immune cells of the brain. These then cluster around disease-associated protein aggregates and help to clear them.
- Jerika J. Barron
- & Anna V. Molofsky
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