Recent studies propose a selective role for SUPT4H1 in the transcription of repeat-containing DNA, the translated products of which contribute to neurodegenerative disorders such as C9orf72-amyotrophic lateral sclerosis.
We demonstrate that HARDEN can be applied to the neurodegenerative disease genes C9orf72 and APP, and methylation can be induced via HDR with both single and double stranded methylated repair templates.
Microtubule-associated protein Tau (MAPT) and GGGGCC (G<sub>4</sub>C<sub>2</sub>) repeat expansion in chromosome 9 open reading frame 72 (C9ORF72) are the major known genetic causes of frontotemporal dementia (FTD) and other neurodegenerative diseases, such as Amyotrophic Lateral Sclerosis (ALS).
We hypothesized that intermediate C9orf72 repeats are a genetic risk factor for corticobasal degeneration (CBD), a neurodegenerative disease that can be clinically similar to Parkinson's but has distinct tau protein pathology.
The intronic hexanucleotide expansion in the C9orf72 gene is one of the leading causes of frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS), two devastating neurodegenerative diseases.
The case reported here raises the question of whether C9orf72 repeat expansion may be involved in neuropsychiatric syndromes beyond the spectrum of neurodegenerative disease.
Repeat expansion in the C9orf72 gene is the most common cause of the neurodegenerative disorder amyotrophic lateral sclerosis (C9-ALS) and is linked to the unconventional translation of five dipeptide-repeat polypeptides (DPRs).
We performed a genetic screen for regulators of RAN translation and identified small ribosomal protein subunit 25 (RPS25), presenting a potential therapeutic target for C9orf72-related amyotrophic lateral sclerosis and frontotemporal dementia and other neurodegenerative diseases caused by nucleotide repeat expansions.
Mutations in genes coding for proteins involved in DNA damage response (DDR) and repair, such as C9orf72 and FUS (Fused in Sarcoma), are associated with neurodegenerative diseases and lead to amyotrophic lateral sclerosis (ALS).
Inclusion of the C9orf72 genetic test in the molecular panels for Brazilian populations with these neurodegenerative diseases should be strongly considered.
We report here that C9orf72, which is linked to the most common forms of the neurodegenerative diseases amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), is a key regulator of lipid metabolism under stress.
This study highlights the importance of the evaluation of ubiquitin/p62-positive cytoplasmic inclusions in all neurodegenerative diseases as a good screening method for the detection of C9orf72 expansion mutation, since this mutation is not rare and can overlap with other neurodegenerative entities.
Massive expansion of a DNA hexanucleotide sequence repeat (C2G4) within the human C9orf72 gene has been linked to a number of neurodegenerative diseases.
We performed genetic testing consisting of C9orf72 hexanucleotide expansion, ATXN2 polyglutamine (polyQ) expansion, and targeted next generation sequencing using the ONDRISeq, a gene panel consisting of 80 genes known to be associated with neurodegenerative diseases such as ALS, FTD, Alzheimer's disease, Parkinson's disease, and vascular cognitive impairment.
Our findings identify a link between stress granule assembly and nucleocytoplasmic transport, two fundamental cellular processes implicated in the pathogenesis of C9ORF72-mediated ALS/FTD and other neurodegenerative diseases.
A hexanucleotide repeat expansion in the C9orf72 gene is the most common cause of inherited forms of the neurodegenerative disease amyotrophic lateral sclerosis (ALS).
Abnormal expansion of hexanucleotide GGGGCC (G<sub>4</sub>C<sub>2</sub>) in the C9ORF72 gene has been associated with multiple neurodegenerative disorders, with particularly high prevalence in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD).
Although large expansions of the non-coding GGGGCC repeat in C9orf72 gene are clearly defined as pathogenic for Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Lobar Degeneration (FTLD), intermediate-length expansions have also been associated with those and other neurodegenerative diseases.
A genetic mutation in the C9orf72 gene causes the most common forms of neurodegenerative diseases amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD).
In this manuscript, we review what is known regarding the autophagic mechanism and discuss the involvement of TDP-43 and C9orf72 in autophagy and their impact on neurodegenerative diseases.
This study is an extensive characterization of iPSC-derived motor neurons as cellular models of ALS carrying C9orf72 hexanucleotide repeats, which describes a novel pathogenic link between C9orf72 mutations, dysregulation of calcium signaling, and altered proteostasis and provides a potential pharmacological target for the treatment of ALS and the related neurodegenerative disease frontotemporal dementia.Stem Cells 2016;34:2063-2078.