Decoding ALS: from genes to mechanism

Mechanisms of FUS mutations in familial amyotrophic lateral sclerosis

(2016) Yulei Shang et al.   BRAIN RESEARCH

C9orf72 Dipeptide Repeats Impair the Assembly, Dynamics, and Function of Membrane-Less Organelles

(2016) Kyung-Ha Lee et al.   CELL

Toxic PR Poly-Dipeptides Encoded by the C9orf72 Repeat Expansion Target LC Domain Polymers

(2016) Yi Lin et al.   CELL

Loss of C9ORF72 impairs autophagy and synergizes with polyQ Ataxin‐2 to induce motor neuron dysfunction and cell death

(2016) Chantal Sellier et al.   EMBO JOURNAL

The C9orf72 protein interacts with Rab1a and the ULK1 complex to regulate initiation of autophagy

(2016) Christopher P Webster et al.   EMBO JOURNAL

TDP-43 binds and transports G-quadruplex-containing mRNAs into neurites for local translation

(2016) Akira Ishiguro et al.   GENES TO CELLS

Directly converted patient-specific induced neurons mirror the neuropathology of FUS with disrupted nuclear localization in amyotrophic lateral sclerosis

(2016) Su Min Lim et al.   Molecular Neurodegeneration

C9ORF72 poly(GA) aggregates sequester and impair HR23 and nucleocytoplasmic transport proteins

(2016) Yong-Jie Zhang et al.   NATURE NEUROSCIENCE

C9orf72 BAC Mouse Model with Motor Deficits and Neurodegenerative Features of ALS/FTD

(2016) Yuanjing Liu et al.   NEURON

Gain of Toxicity from ALS/FTD-Linked Repeat Expansions in C9ORF72 Is Alleviated by Antisense Oligonucleotides Targeting GGGGCC-Containing RNAs

(2016) Jie Jiang et al.   NEURON

C9orf72 is required for proper macrophage and microglial function in mice

(2016) J. G. ORourke et al.   SCIENCE

Loss-of-function mutations in the C9ORF72 mouse ortholog cause fatal autoimmune disease

(2016) Aaron Burberry et al.   Science Translational Medicine

C9orf72 ablation causes immune dysregulation characterized by leukocyte expansion, autoantibody production and glomerulonephropathy in mice

(2016) Amanda Atanasio et al.   Scientific Reports

Antisense RNA foci in the motor neurons of C9ORF72-ALS patients are associated with TDP-43 proteinopathy

(2015) Johnathan Cooper-Knock et al.   ACTA NEUROPATHOLOGICA

Quantitative analysis and clinico-pathological correlations of different dipeptide repeat protein pathologies in C9ORF72 mutation carriers

(2015) Ian R. A. Mackenzie et al.   ACTA NEUROPATHOLOGICA

Prion-like propagation of mutant SOD1 misfolding and motor neuron disease spread along neuroanatomical pathways

(2015) Jacob I. Ayers et al.   ACTA NEUROPATHOLOGICA

Distribution of dipeptide repeat proteins in cellular models and C9orf72 mutation cases suggests link to transcriptional silencing

(2015) Martin H. Schludi et al.   ACTA NEUROPATHOLOGICA

C9orf72 ablation in mice does not cause motor neuron degeneration or motor deficits

(2015) Max Koppers et al.   ANNALS OF NEUROLOGY

Phase Separation by Low Complexity Domains Promotes Stress Granule Assembly and Drives Pathological Fibrillization

(2015) Amandine Molliex et al.   CELL

A Liquid-to-Solid Phase Transition of the ALS Protein FUS Accelerated by Disease Mutation

(2015) Avinash Patel et al.   CELL

Dysregulated miRNA biogenesis downstream of cellular stress and ALS-causing mutations: a new mechanism for ALS

(2015) A. Emde et al.   EMBO JOURNAL

Formation and Maturation of Phase-Separated Liquid Droplets by RNA-Binding Proteins

(2015) Yuan Lin et al.   MOLECULAR CELL

The C9orf72 repeat expansion disrupts nucleocytoplasmic transport

(2015) Ke Zhang et al.   NATURE

GGGGCC repeat expansion in C9orf72 compromises nucleocytoplasmic transport

(2015) Brian D. Freibaum et al.   NATURE

Haploinsufficiency of TBK1 causes familial ALS and fronto-temporal dementia

(2015) Axel Freischmidt et al.   NATURE NEUROSCIENCE

Modifiers of C9orf72 dipeptide repeat toxicity connect nucleocytoplasmic transport defects to FTD/ALS

(2015) Ana Jovičić et al.   NATURE NEUROSCIENCE

ALS/FTD Mutation-Induced Phase Transition of FUS Liquid Droplets and Reversible Hydrogels into Irreversible Hydrogels Impairs RNP Granule Function

(2015) Tetsuro Murakami et al.   NEURON

Human C9ORF72 Hexanucleotide Expansion Reproduces RNA Foci and Dipeptide Repeat Proteins but Not Neurodegeneration in BAC Transgenic Mice

(2015) Owen M. Peters et al.   NEURON

C9orf72 BAC Transgenic Mice Display Typical Pathologic Features of ALS/FTD

(2015) Jacqueline G. O’Rourke et al.   NEURON

C9ORF72 repeat expansions in mice cause TDP-43 pathology, neuronal loss, and behavioral deficits

(2015) J. Chew et al.   SCIENCE

TDP-43 repression of nonconserved cryptic exons is compromised in ALS-FTD

(2015) J. P. Ling et al.   SCIENCE

Endogenous retroviruses in ALS: A reawakening?

(2015) Robert H. Brown et al.   Science Translational Medicine

Aggregation-prone c9FTD/ALS poly(GA) RAN-translated proteins cause neurotoxicity by inducing ER stress

(2014) Yong-Jie Zhang et al.   ACTA NEUROPATHOLOGICA

Liquid-Liquid Phase Separation in Biology

(2014) Anthony A. Hyman et al.   Annual Review of Cell and Developmental Biology

A mitochondrial origin for frontotemporal dementia and amyotrophic lateral sclerosis through CHCHD10 involvement

(2014) Sylvie Bannwarth et al.   BRAIN

Characterization of the dipeptide repeat protein in the molecular pathogenesis of c9FTD/ALS

(2014) Mai Yamakawa et al.   HUMAN MOLECULAR GENETICS

MicroRNAs as Potential Circulating Biomarkers for Amyotrophic Lateral Sclerosis

(2014) Frank Cloutier et al.   JOURNAL OF MOLECULAR NEUROSCIENCE

Neurodegenerative diseases: G-quadruplex poses quadruple threat

(2014) J. Paul Taylor   NATURE

C9orf72 nucleotide repeat structures initiate molecular cascades of disease

(2014) Aaron R. Haeusler et al.   NATURE

Mutations in the Matrin 3 gene cause familial amyotrophic lateral sclerosis

(2014) Janel O Johnson et al.   NATURE NEUROSCIENCE

Reduced C9orf72 protein levels in frontal cortex of amyotrophic lateral sclerosis and frontotemporal degeneration brain with the C9ORF72 hexanucleotide repeat expansion

(2014) Adrian J. Waite et al.   NEUROBIOLOGY OF AGING

Antisense Proline-Arginine RAN Dipeptides Linked to C9ORF72-ALS/FTD Form Toxic Nuclear Aggregates that Initiate In Vitro and In Vivo Neuronal Death

(2014) Xinmei Wen et al.   NEURON

Axonal Transport of TDP-43 mRNA Granules Is Impaired by ALS-Causing Mutations

(2014) Nael H. Alami et al.   NEURON

Necroptosis Drives Motor Neuron Death in Models of Both Sporadic and Familial ALS

(2014) Diane B. Re et al.   NEURON

Microglia Induce Motor Neuron Death via the Classical NF-κB Pathway in Amyotrophic Lateral Sclerosis

(2014) Ashley E. Frakes et al.   NEURON

Exome-wide Rare Variant Analysis Identifies TUBA4A Mutations Associated with Familial ALS

(2014) Bradley N. Smith et al.   NEURON

The Role of Muscle microRNAs in Repairing the Neuromuscular Junction

(2014) Gregorio Valdez et al.   PLoS One

C9orf72 repeat expansions cause neurodegeneration in Drosophila through arginine-rich proteins

(2014) S. Mizielinska et al.   SCIENCE

Poly-dipeptides encoded by the C9orf72 repeats bind nucleoli, impede RNA biogenesis, and kill cells

(2014) I. Kwon et al.   SCIENCE

Dipeptide repeat protein pathology in C9ORF72 mutation cases: clinico-pathological correlations

(2013) Ian R. Mackenzie et al.   ACTA NEUROPATHOLOGICA

Bidirectional transcripts of the expanded C9orf72 hexanucleotide repeat are translated into aggregating dipeptide repeat proteins

(2013) Kohji Mori et al.   ACTA NEUROPATHOLOGICA

Antisense transcripts of the expanded C9ORF72 hexanucleotide repeat form nuclear RNA foci and undergo repeat-associated non-ATG translation in c9FTD/ALS

(2013) Tania F. Gendron et al.   ACTA NEUROPATHOLOGICA

Mutations in SQSTM1 encoding p62 in amyotrophic lateral sclerosis: genetics and neuropathology

(2013) Elisa Teyssou et al.   ACTA NEUROPATHOLOGICA

Altered Ribostasis: RNA-Protein Granules in Degenerative Disorders

(2013) Mani Ramaswami et al.   CELL

Enhancing Mitochondrial Calcium Buffering Capacity Reduces Aggregation of Misfolded SOD1 and Motor Neuron Cell Death without Extending Survival in Mouse Models of Inherited Amyotrophic Lateral Sclerosis

(2013) P. A. Parone et al.   JOURNAL OF NEUROSCIENCE

Mutations in prion-like domains in hnRNPA2B1 and hnRNPA1 cause multisystem proteinopathy and ALS

(2013) Hong Joo Kim et al.   NATURE

Self-propagation of pathogenic protein aggregates in neurodegenerative diseases

(2013) Mathias Jucker et al.   NATURE

Degeneration and impaired regeneration of gray matter oligodendrocytes in amyotrophic lateral sclerosis

(2013) Shin H Kang et al.   NATURE NEUROSCIENCE

The epidemiology of ALS: a conspiracy of genes, environment and time

(2013) Ammar Al-Chalabi et al.   Nature Reviews Neurology

Unconventional Translation of C9ORF72 GGGGCC Expansion Generates Insoluble Polypeptides Specific to c9FTD/ALS

(2013) Peter E.A. Ash et al.   NEURON

RNA Toxicity from the ALS/FTD C9ORF72 Expansion Is Mitigated by Antisense Intervention

(2013) Christopher J. Donnelly et al.   NEURON

Downregulation of MicroRNA-9 in iPSC-Derived Neurons of FTD/ALS Patients with TDP-43 Mutations

(2013) Zhijun Zhang et al.   PLoS One

RAN proteins and RNA foci from antisense transcripts in C9ORF72 ALS and frontotemporal dementia

(2013) T. Zu et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Expanded GGGGCC repeat RNA associated with amyotrophic lateral sclerosis and frontotemporal dementia causes neurodegeneration

(2013) Z. Xu et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Targeted degradation of sense and antisense C9orf72 RNA foci as therapy for ALS and frontotemporal degeneration

(2013) C. Lagier-Tourenne et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

The C9orf72 GGGGCC Repeat Is Translated into Aggregating Dipeptide-Repeat Proteins in FTLD/ALS

(2013) K. Mori et al.   SCIENCE

Targeting RNA Foci in iPSC-Derived Motor Neurons from ALS Patients with a C9ORF72 Repeat Expansion

(2013) D. Sareen et al.   Science Translational Medicine

Hexanucleotide Repeats in ALS/FTD Form Length-Dependent RNA Foci, Sequester RNA Binding Proteins, and Are Neurotoxic

(2013) Youn-Bok Lee et al.   Cell Reports

Clinico-pathological features in amyotrophic lateral sclerosis with expansions in C9ORF72

(2012) Johnathan Cooper-Knock et al.   BRAIN

Oligodendroglia metabolically support axons and contribute to neurodegeneration

(2012) Youngjin Lee et al.   NATURE

Mutations in the profilin 1 gene cause familial amyotrophic lateral sclerosis

(2012) Chi-Hong Wu et al.   NATURE

EPHA4 is a disease modifier of amyotrophic lateral sclerosis in animal models and in humans

(2012) Annelies Van Hoecke et al.   NATURE MEDICINE

Divergent roles of ALS-linked proteins FUS/TLS and TDP-43 intersect in processing long pre-mRNAs

(2012) Clotilde Lagier-Tourenne et al.   NATURE NEUROSCIENCE

Integrative Genome-wide Analysis Reveals Cooperative Regulation of Alternative Splicing by hnRNP Proteins

(2012) Stephanie C. Huelga et al.   Cell Reports

p62 positive, TDP-43 negative, neuronal cytoplasmic and intranuclear inclusions in the cerebellum and hippocampus define the pathology of C9orf72-linked FTLD and MND/ALS

(2011) Safa Al-Sarraj et al.   ACTA NEUROPATHOLOGICA

SQSTM1 Mutations in Familial and Sporadic Amyotrophic Lateral Sclerosis

(2011) Faisal Fecto   ARCHIVES OF NEUROLOGY

Mutations in UBQLN2 cause dominant X-linked juvenile and adult-onset ALS and ALS/dementia

(2011) Han-Xiang Deng et al.   NATURE

Astrocytes from familial and sporadic ALS patients are toxic to motor neurons

(2011) Amanda M Haidet-Phillips et al.   NATURE BIOTECHNOLOGY

Long pre-mRNA depletion and RNA missplicing contribute to neuronal vulnerability from loss of TDP-43

(2011) Magdalini Polymenidou et al.   NATURE NEUROSCIENCE

Characterizing the RNA targets and position-dependent splicing regulation by TDP-43

(2011) James R Tollervey et al.   NATURE NEUROSCIENCE

Expanded GGGGCC Hexanucleotide Repeat in Noncoding Region of C9ORF72 Causes Chromosome 9p-Linked FTD and ALS

(2011) Mariely DeJesus-Hernandez et al.   NEURON

A Hexanucleotide Repeat Expansion in C9ORF72 Is the Cause of Chromosome 9p21-Linked ALS-FTD

(2011) Alan E. Renton et al.   NEURON

Intermolecular transmission of superoxide dismutase 1 misfolding in living cells

(2011) L. I. Grad et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Prion-like propagation of mutant superoxide dismutase-1 misfolding in neuronal cells

(2011) Christian Münch et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Phosphorylation of the Autophagy Receptor Optineurin Restricts Salmonella Growth

(2011) P. Wild et al.   SCIENCE

Astrocyte loss of mutant SOD1 delays ALS disease onset and progression in G85R transgenic mice

(2010) L. Wang et al.   HUMAN MOLECULAR GENETICS

TDP-43 and FUS/TLS: emerging roles in RNA processing and neurodegeneration

(2010) C. Lagier-Tourenne et al.   HUMAN MOLECULAR GENETICS

Characterization of the Properties of a Novel Mutation in VAPB in Familial Amyotrophic Lateral Sclerosis

(2010) Han-Jou Chen et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Chromosome 9p21 in amyotrophic lateral sclerosis in Finland: a genome-wide association study

(2010) Hannu Laaksovirta et al.   LANCET NEUROLOGY

Chromosome 9p21 in sporadic amyotrophic lateral sclerosis in the UK and seven other countries: a genome-wide association study

(2010) Aleksey Shatunov et al.   LANCET NEUROLOGY

Ataxin-2 intermediate-length polyglutamine expansions are associated with increased risk for ALS

(2010) Andrew C. Elden et al.   NATURE

Mutations of optineurin in amyotrophic lateral sclerosis

(2010) Hirofumi Maruyama et al.   NATURE

Common variants at 7p21 are associated with frontotemporal lobar degeneration with TDP-43 inclusions

(2010) Vivianna M Van Deerlin et al.   NATURE GENETICS

Repeat expansion disease: progress and puzzles in disease pathogenesis

(2010) Albert R. La Spada et al.   NATURE REVIEWS GENETICS

TDP43-Positive Intraneuronal Inclusions in a Patient with Motor Neuron Disease and Parkinson’s Disease

(2010) Jean-Baptiste Chanson et al.   Neurodegenerative Diseases

Exome Sequencing Reveals VCP Mutations as a Cause of Familial ALS

(2010) Janel O. Johnson et al.   NEURON

Non-ATG-initiated translation directed by microsatellite expansions

(2010) T. Zu et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Transactive Response DNA-Binding Protein 43 Burden in Familial Alzheimer Disease and Down Syndrome

(2009) Carol F. Lippa et al.   ARCHIVES OF NEUROLOGY

A Switch in Retrograde Signaling from Survival to Stress in Rapid-Onset Neurodegeneration

(2009) E. Perlson et al.   JOURNAL OF NEUROSCIENCE

Sarcoplasmic redistribution of nuclear TDP-43 in inclusion body myositis

(2009) Mohammad Salajegheh et al.   MUSCLE & NERVE

Genome-wide association study identifies 19p13.3 (UNC13A) and 9p21.2 as susceptibility loci for sporadic amyotrophic lateral sclerosis

(2009) Michael A van Es et al.   NATURE GENETICS

A role for motoneuron subtype–selective ER stress in disease manifestations of FALS mice

(2009) Smita Saxena et al.   NATURE NEUROSCIENCE

ALS motor phenotype heterogeneity, focality, and spread: Deconstructing motor neuron degeneration

(2009) J. M. Ravits et al.   NEUROLOGY

MicroRNA-206 Delays ALS Progression and Promotes Regeneration of Neuromuscular Synapses in Mice

(2009) A. H. Williams et al.   SCIENCE

Mutations in FUS, an RNA Processing Protein, Cause Familial Amyotrophic Lateral Sclerosis Type 6

(2009) C. Vance et al.   SCIENCE

Mutations in the FUS/TLS Gene on Chromosome 16 Cause Familial Amyotrophic Lateral Sclerosis

(2009) T. J. Kwiatkowski et al.   SCIENCE

Non-Cell-Autonomous Effect of Human SOD1G37R Astrocytes on Motor Neurons Derived from Human Embryonic Stem Cells

(2008) Maria C.N. Marchetto et al.   Cell Stem Cell

ALS-linked mutant SOD1 induces ER stress- and ASK1-dependent motor neuron death by targeting Derlin-1

(2008) H. Nishitoh et al.   GENES & DEVELOPMENT

TARDBP mutations in individuals with sporadic and familial amyotrophic lateral sclerosis

(2008) Edor Kabashi et al.   NATURE GENETICS

Focal transplantation–based astrocyte replacement is neuroprotective in a model of motor neuron disease

(2008) Angelo C Lepore et al.   NATURE NEUROSCIENCE

Astrocytes as determinants of disease progression in inherited amyotrophic lateral sclerosis

(2008) Koji Yamanaka et al.   NATURE NEUROSCIENCE

Mutant SOD1 in cell types other than motor neurons and oligodendrocytes accelerates onset of disease in ALS mice

(2008) K. Yamanaka et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

TDP-43 Mutations in Familial and Sporadic Amyotrophic Lateral Sclerosis

(2008) J. Sreedharan et al.   SCIENCE