23 Result(s)
within
Clotilde Lagier-Tourenne
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Article
Open AccessNeuronal STING activation in amyotrophic lateral sclerosis and frontotemporal dementia
The stimulator of interferon genes (STING) pathway has been implicated in neurodegenerative diseases, including Parkinson’s disease and amyotrophic lateral sclerosis (ALS). While prior studies have focused on ...
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Article
Open AccessCryptic splicing of stathmin-2 and UNC13A mRNAs is a pathological hallmark of TDP-43-associated Alzheimer’s disease
Nuclear clearance and cytoplasmic accumulations of the RNA-binding protein TDP-43 are pathological hallmarks in almost all patients with amyotrophic lateral sclerosis (ALS) and up to 50% of patients with front...
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Article
Stathmin-2 loss leads to neurofilament-dependent axonal collapse driving motor and sensory denervation
The mRNA transcript of the human STMN2 gene, encoding for stathmin-2 protein (also called SCG10), is profoundly impacted by TAR DNA-binding protein 43 (TDP-43) loss of function. The latter is a hallmark of severa...
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Open AccessWild-type FUS corrects ALS-like disease induced by cytoplasmic mutant FUS through autoregulation
Mutations in FUS, an RNA-binding protein involved in multiple steps of RNA metabolism, are associated with the most severe forms of amyotrophic lateral sclerosis (ALS). Accumulation of cytoplasmic FUS is likel...
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Open AccessCytoplasmic FUS triggers early behavioral alterations linked to cortical neuronal hyperactivity and inhibitory synaptic defects
Gene mutations causing cytoplasmic mislocalization of the RNA-binding protein FUS lead to severe forms of amyotrophic lateral sclerosis (ALS). Cytoplasmic accumulation of FUS is also observed in other diseases...
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Article
Reduced C9ORF72 function exacerbates gain of toxicity from ALS/FTD-causing repeat expansion in C9orf72
Hexanucleotide expansions in C9orf72, which encodes a predicted guanine exchange factor, are the most frequent genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Although repe...
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FUS-mediated regulation of acetylcholine receptor transcription at neuromuscular junctions is compromised in amyotrophic lateral sclerosis
Neuromuscular junction (NMJ) disruption is an early pathogenic event in amyotrophic lateral sclerosis (ALS). Yet, direct links between NMJ pathways and ALS-associated genes such as FUS, whose heterozygous mutatio...
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Premature polyadenylation-mediated loss of stathmin-2 is a hallmark of TDP-43-dependent neurodegeneration
Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are associated with loss of nuclear transactive response DNA-binding protein 43 (TDP-43). Here we identify that TDP-43 regulates expression...
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Animal models of neurodegenerative diseases
Animal models of adult-onset neurodegenerative diseases have enhanced the understanding of the molecular pathogenesis of Alzheimer’s disease, Parkinson’s disease, frontotemporal dementia, and amyotrophic later...
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Article
Nuclear pores: the gate to neurodegeneration
Compromised compartmentalization of nucleus and cytoplasm has emerged as a central feature of aging and neurodegenerative diseases. Nucleocytoplasmic transport is disrupted, with widespread mislocalization of ...
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Article
Open AccessCUG initiation and frameshifting enable production of dipeptide repeat proteins from ALS/FTD C9ORF72 transcripts
Expansion of G4C2 repeats in the C9ORF72 gene is the most prevalent inherited form of amyotrophic lateral sclerosis and frontotemporal dementia. Expanded transcripts undergo repeat-associated non-AUG (RAN) transl...
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Open AccessMotor neuron intrinsic and extrinsic mechanisms contribute to the pathogenesis of FUS-associated amyotrophic lateral sclerosis
Motor neuron-extrinsic mechanisms have been shown to participate in the pathogenesis of ALS-SOD1, one familial form of amyotrophic lateral sclerosis (ALS). It remains unclear whether such mechanisms contribute...
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Article
C9ORF72 poly(GA) aggregates sequester and impair HR23 and nucleocytoplasmic transport proteins
Zhang et al. show that the poly(GA) proteins produced in patients with C9ORF72 repeat expansions cause neurodegeneration and behavioral abnormalities when expressed in mice. The emergence of these phenotypes requ...
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Novel clinical associations with specific C9ORF72 transcripts in patients with repeat expansions in C9ORF72
The loss of chromosome 9 open reading frame 72 (C9ORF72) expression, associated with C9ORF72 repeat expansions, has not been examined systematically. Three C9ORF72 transcript variants have been described thus far...
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Open AccessCerebellar c9RAN proteins associate with clinical and neuropathological characteristics of C9ORF72 repeat expansion carriers
Clinical and neuropathological characteristics associated with G4C2 repeat expansions in chromosome 9 open reading frame 72 (C9ORF72), the most common genetic cause of amyotrophic lateral sclerosis (ALS) and fron...
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ALS-causative mutations in FUS/TLS confer gain and loss of function by altered association with SMN and U1-snRNP
The RNA-binding protein FUS/TLS, mutation in which is causative of the fatal motor neuron disease amyotrophic lateral sclerosis (ALS), is demonstrated to directly bind to the U1-snRNP and SMN complexes. ALS-ca...
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Article
Mutant Huntingtin promotes autonomous microglia activation via myeloid lineage-determining factors
In this study, the authors show that cell-autonomous expression of mutant Huntingtin in microglia can elicit alterations in the transcriptional profile and activation state of the cells. In particular, there i...
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Divergent roles of ALS-linked proteins FUS/TLS and TDP-43 intersect in processing long pre-mRNAs
In this study, the authors compare the RNA binding patterns of FUS/TLS and TDP-43. Although these proteins regulate the processing of mostly distinct gene products, they do show concurrent regulation of a subs...
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Article
Long pre-mRNA depletion and RNA missplicing contribute to neuronal vulnerability from loss of TDP-43
The authors identify brain RNA targets for TDP-43, a RNA binding protein linked to ALS. RNAs derived from genes with very long introns were more affected by TDP-43 levels. TDP-43 also auto-regulated its own sy...
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An expansion in ALS genetics
Aggregates and mutations of the proteins ataxin-2 and TDP-43 have been implicated in distinct neurodegenerative disorders. An interplay between these proteins is now reported for amyotrophic lateral sclerosis.
