Insights into the pathogenic mechanisms of Chromosome 9 open reading frame 72 (C9orf72) repeat expansions

An amyloid-like cascade hypothesis for C9orf72 ALS/FTD

(2016) Dieter Edbauer et al.   CURRENT OPINION IN NEUROBIOLOGY

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

Cerebellar c9RAN proteins associate with clinical and neuropathological characteristics of C9ORF72 repeat expansion carriers

(2015) Tania F. Gendron et al.   ACTA NEUROPATHOLOGICA

A 30-unit hexanucleotide repeat expansion in C9orf72 induces pathological lesions with dipeptide-repeat proteins and RNA foci, but not TDP-43 inclusions and clinical disease

(2015) Priya Gami 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

Novel clinical associations with specific C9ORF72 transcripts in patients with repeat expansions in C9ORF72

(2015) Marka van Blitterswijk 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

FTD/ALS-associated poly(GR) protein impairs the Notch pathway and is recruited by poly(GA) into cytoplasmic inclusions

(2015) Dejun Yang et al.   ACTA NEUROPATHOLOGICA

Isoform-specific antibodies reveal distinct subcellular localizations of C9orf72 in amyotrophic lateral sclerosis

(2015) Shangxi Xiao et al.   ANNALS OF NEUROLOGY

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

Directly Reprogrammed Human Neurons Retain Aging-Associated Transcriptomic Signatures and Reveal Age-Related Nucleocytoplasmic Defects

(2015) Jerome Mertens et al.   Cell Stem Cell

Nucleolar stress and impaired stress granule formation contribute to C9orf72 RAN translation-induced cytotoxicity

(2015) Zhouteng Tao et al.   HUMAN MOLECULAR GENETICS

Profiling of Ubiquitination Pathway Genes in Peripheral Cells from Patients with Frontotemporal Dementia due to C9ORF72 and GRN Mutations

(2015) Maria Serpente et al.   INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

Nuclear accumulation of mRNAs underlies G4C2-repeat-induced translational repression in a cellular model of C9orf72 ALS

(2015) S. Rossi et al.   JOURNAL OF CELL SCIENCE

Motor neuron dysfunctions in the frontotemporal lobar degeneration spectrum: A clinical and neurophysiological study

(2015) C. Cerami et al.   JOURNAL OF THE NEUROLOGICAL SCIENCES

Presymptomatic cognitive and neuroanatomical changes in genetic frontotemporal dementia in the Genetic Frontotemporal dementia Initiative (GENFI) study: a cross-sectional analysis

(2015) Jonathan D Rohrer et al.   LANCET NEUROLOGY

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

Distinct brain transcriptome profiles in C9orf72-associated and sporadic ALS

(2015) Mercedes Prudencio et al.   NATURE NEUROSCIENCE

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

(2015) Ana Jovičić et al.   NATURE NEUROSCIENCE

Characterization of DNA G-quadruplex species forming from C9ORF72 G4C2-expanded repeats associated with amyotrophic lateral sclerosis and frontotemporal lobar degeneration

(2015) Primož Šket et al.   NEUROBIOLOGY OF AGING

C9orf72 promoter hypermethylation is neuroprotective: Neuroimaging and neuropathologic evidence

(2015) C. T. McMillan et al.   NEUROLOGY

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

Differential Toxicity of Nuclear RNA Foci versus Dipeptide Repeat Proteins in a Drosophila Model of C9ORF72 FTD/ALS

(2015) Helene Tran et al.   NEURON

Clinicopathological description of two cases withSQSTM1gene mutation associated with frontotemporal dementia

(2015) Gabor G. Kovacs et al.   NEUROPATHOLOGY

Accumulation of dipeptide repeat proteins predates that of TDP-43 in frontotemporal lobar degeneration associated with hexanucleotide repeat expansions inC9ORF72gene

(2015) Atik Baborie et al.   NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY

Neurodegeneration in frontotemporal lobar degeneration and motor neurone disease associated with expansions inC9orf72is linked to TDP-43 pathology and not associated with aggregated forms of dipeptide repeat proteins

(2015) Y. Davidson et al.   NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY

G-quadruplexes and their regulatory roles in biology

(2015) Daniela Rhodes et al.   NUCLEIC ACIDS RESEARCH

Cytoplasmic protein aggregates interfere with nucleocytoplasmic transport of protein and RNA

(2015) A. C. Woerner et al.   SCIENCE

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

(2015) J. Chew et al.   SCIENCE

Human iPSC-derived motoneurons harbouring TARDBP or C9ORF72 ALS mutations are dysfunctional despite maintaining viability

(2015) Anna-Claire Devlin et al.   Nature Communications

Axonal Ion Channel Dysfunction inC9orf72Familial Amyotrophic Lateral Sclerosis

(2015) Nimeshan Geevasinga et al.   JAMA Neurology

Dipeptide repeat protein inclusions are rare in the spinal cord and almost absent from motor neurons in C9ORF72 mutant amyotrophic lateral sclerosis and are unlikely to cause their degeneration

(2015) Jorge Gomez-Deza et al.   Acta Neuropathologica Communications

C9ORF72 GGGGCC Expanded Repeats Produce Splicing Dysregulation which Correlates with Disease Severity in Amyotrophic Lateral Sclerosis

(2015) Johnathan Cooper-Knock et al.   PLoS One

Early dipeptide repeat pathology in a frontotemporal dementia kindred with C9ORF72 mutation and intellectual disability

(2014) Malcolm Proudfoot et al.   ACTA NEUROPATHOLOGICA

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

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

C9orf72 FTLD/ALS-associated Gly-Ala dipeptide repeat proteins cause neuronal toxicity and Unc119 sequestration

(2014) Stephanie May et al.   ACTA NEUROPATHOLOGICA

Hypermethylation of repeat expanded C9orf72 is a clinical and molecular disease modifier

(2014) Jenny Russ et al.   ACTA NEUROPATHOLOGICA

C9orf72 hypermethylation protects against repeat expansion-associated pathology in ALS/FTD

(2014) Elaine Y. Liu et al.   ACTA NEUROPATHOLOGICA

Sequestration of multiple RNA recognition motif-containing proteins by C9orf72 repeat expansions

(2014) Johnathan Cooper-Knock et al.   BRAIN

Characterization of DNA hypermethylation in the cerebellum of c9FTD/ALS patients

(2014) Veronique V. Belzil et al.   BRAIN RESEARCH

Rab proteins: The key regulators of intracellular vesicle transport

(2014) Tanmay Bhuin et al.   EXPERIMENTAL CELL RESEARCH

Hypermethylation of the CpG-island near the C9orf72 G4C2-repeat expansion in FTLD patients

(2014) Zhengrui Xi et al.   HUMAN MOLECULAR GENETICS

C9ORF72, implicated in amytrophic lateral sclerosis and frontotemporal dementia, regulates endosomal trafficking

(2014) Manal A. Farg et al.   HUMAN MOLECULAR GENETICS

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

(2014) Mai Yamakawa et al.   HUMAN MOLECULAR GENETICS

Ubiquilin 2: A component of the ubiquitin–proteasome system with an emerging role in neurodegeneration

(2014) Katharine Y. Zhang et al.   INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY

C9orf72 nucleotide repeat structures initiate molecular cascades of disease

(2014) Aaron R. Haeusler et al.   NATURE

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

Discovery of a Biomarker and Lead Small Molecules to Target r(GGGGCC)-Associated Defects in c9FTD/ALS

(2014) Zhaoming Su et al.   NEURON

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

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

Intrinsic Membrane Hyperexcitability of Amyotrophic Lateral Sclerosis Patient-Derived Motor Neurons

(2014) Brian J. Wainger et al.   Cell Reports

The Role of the Selective Adaptor p62 and Ubiquitin-Like Proteins in Autophagy

(2014) Mónika Lippai et al.   Biomed Research International

RETRACTED ARTICLE: A new inducible transgenic mouse model for C9orf72-associated GGGGCC repeat expansion supports a gain-of-function mechanism in C9orf72-associated ALS and FTD

(2014) Renate K Hukema et al.   Acta Neuropathologica Communications

Brain distribution of dipeptide repeat proteins in frontotemporal lobar degeneration and motor neurone disease associated with expansions in C9ORF72

(2014) Yvonne S Davidson et al.   Acta Neuropathologica Communications

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

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

Homozygosity for the C9orf72 GGGGCC repeat expansion in frontotemporal dementia

(2013) Pietro Fratta et al.   ACTA NEUROPATHOLOGICA

C9orf72 frontotemporal lobar degeneration is characterised by frequent neuronal sense and antisense RNA foci

(2013) Sarah Mizielinska 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

hnRNP A3 binds to GGGGCC repeats and is a constituent of p62-positive/TDP43-negative inclusions in the hippocampus of patients with C9orf72 mutations

(2013) Kohji Mori et al.   ACTA NEUROPATHOLOGICA

Reduced C9orf72 gene expression in c9FTD/ALS is caused by histone trimethylation, an epigenetic event detectable in blood

(2013) Veronique V. Belzil et al.   ACTA NEUROPATHOLOGICA

Modeling key pathological features of frontotemporal dementia with C9ORF72 repeat expansion in iPSC-derived human neurons

(2013) Sandra Almeida et al.   ACTA NEUROPATHOLOGICA

The product of C9orf72, a gene strongly implicated in neurodegeneration, is structurally related to DENN Rab-GEFs

(2013) Timothy P. Levine et al.   BIOINFORMATICS

The Disease-associated r(GGGGCC)nRepeat from theC9orf72Gene Forms Tract Length-dependent Uni- and Multimolecular RNA G-quadruplex Structures

(2013) Kaalak Reddy et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Stress granules as crucibles of ALS pathogenesis

(2013) Yun R. Li et al.   JOURNAL OF CELL BIOLOGY

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

(2013) Hong Joo Kim et al.   NATURE

Lack of C9ORF72 coding mutations supports a gain of function for repeat expansions in amyotrophic lateral sclerosis

(2013) Matthew B. Harms et al.   NEUROBIOLOGY OF AGING

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

Deletion of C9ORF72 Results in Motor Neuron Degeneration and Stress Sensitivity in C. elegans

(2013) Martine Therrien 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

Dipeptide repeat proteins are present in the p62 positive inclusions in patients with frontotemporal lobar degeneration and motor neurone disease associated with expansions in C9ORF72

(2013) David MA Mann et al.   Acta Neuropathologica Communications

Pattern of ubiquilin pathology in ALS and FTLD indicates presence of C9ORF72 hexanucleotide expansion

(2012) Johannes Brettschneider et al.   ACTA NEUROPATHOLOGICA

Tau pathology in frontotemporal lobar degeneration with C9ORF72 hexanucleotide repeat expansion

(2012) Kevin F. Bieniek et al.   ACTA NEUROPATHOLOGICA

Clinical and pathological features of amyotrophic lateral sclerosis caused by mutation in the C9ORF72 gene on chromosome 9p

(2012) Heather Stewart et al.   ACTA NEUROPATHOLOGICA

Clinical and pathological features of familial frontotemporal dementia caused by C9ORF72 mutation on chromosome 9p

(2012) G.-Y. R. Hsiung et al.   BRAIN

Distinct clinical and pathological characteristics of frontotemporal dementia associated with C9ORF72 mutations

(2012) J. S. Snowden et al.   BRAIN

Neuroimaging signatures of frontotemporal dementia genetics: C9ORF72, tau, progranulin and sporadics

(2012) J. L. Whitwell et al.   BRAIN

Cell-free Formation of RNA Granules: Low Complexity Sequence Domains Form Dynamic Fibers within Hydrogels

(2012) Masato Kato et al.   CELL

Frequency of the C9orf72 hexanucleotide repeat expansion in patients with amyotrophic lateral sclerosis and frontotemporal dementia: a cross-sectional study

(2012) Elisa Majounie et al.   LANCET NEUROLOGY

Frontotemporal dementia due to C9ORF72 mutations: Clinical and imaging features

(2012) S. J. Sha et al.   NEUROLOGY

C9orf72 hexanucleotide repeat associated with amyotrophic lateral sclerosis and frontotemporal dementia forms RNA G-quadruplexes

(2012) Pietro Fratta et al.   Scientific Reports

Longitudinal neuroimaging and neuropsychological profiles of frontotemporal dementia with C9ORF72 expansions

(2012) Colin J Mahoney et al.   Alzheimers Research & Therapy

Discovery of Novel DENN Proteins: Implications for the Evolution of Eukaryotic Intracellular Membrane Structures and Human Disease

(2012) Dapeng Zhang et al.   Frontiers in Genetics

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

Proteasome inhibitor MG132-induced apoptosis via ER stress-mediated apoptotic pathway and its potentiation by protein tyrosine kinase p56lck in human Jurkat T cells

(2011) Hae Sun Park et al.   BIOCHEMICAL PHARMACOLOGY

A C9orf72 promoter repeat expansion in a Flanders-Belgian cohort with disorders of the frontotemporal lobar degeneration-amyotrophic lateral sclerosis spectrum: a gene identification study

(2011) Ilse Gijselinck et al.   LANCET NEUROLOGY

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

(2011) Han-Xiang Deng et al.   NATURE

UNC119 is required for G protein trafficking in sensory neurons

(2011) Houbin Zhang 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

Cell-autonomous and non-cell-autonomous toxicity in polyglutamine diseases

(2011) Fabio Sambataro et al.   PROGRESS IN NEUROBIOLOGY