A hexanucleotide (G4C2) repeat expansion in the 5' non-coding region C9orf72 is the most common genetic cause of amyotrophic lateral sclerosis and frontotemporal lobar degeneration. Three modes of toxicity have been proposed: gain of function through formation of RNA foci and sequestration of RNA binding proteins; expression of dipeptide repeat proteins generated by repeat-associated non-ATG translation; and loss of function due to C9orf72 haploinsufficiency. Much is known about the proposed gain of function mechanisms, but there is little knowledge of the normal function of C9orf72 and the cellular consequences if its activity is perturbed. Here we will review what is known of C9orf72 at the transcript and protein levels and how changes in C9orf72 expression could contribute to disease pathogenesis. This article is part of a Special Issue entitled SI:RNA Metabolism in Disease.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.brainres.2016.04.062 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
NS1 binding protein regulates stress granule dynamics and clearance by inhibiting p62 ubiquitination.
Nat Commun
December 2024
Department of Biological Sciences and Biotechnology, College of Life Sciences and Nanotechnology, Hannam University, Daejeon, Korea.
The NS1 binding protein, known for interacting with the influenza A virus protein, is involved in RNA processing, cancer, and nerve cell growth regulation. However, its role in stress response independent of viral infections remains unclear. This study investigates NS1 binding protein's function in regulating stress granules during oxidative stress through interactions with GABARAP subfamily proteins.
View Article and Find Full Text PDFLocalized molecular chaperone synthesis maintains neuronal dendrite proteostasis.
Nat Commun
December 2024
Department of Biochemistry, McGill University, Montreal, QC, Canada.
Proteostasis is maintained through regulated protein synthesis and degradation and chaperone-assisted protein folding. However, this is challenging in neuronal projections because of their polarized morphology and constant synaptic proteome remodeling. Using high-resolution fluorescence microscopy, we discover that hippocampal and spinal cord motor neurons of mouse and human origin localize a subset of chaperone mRNAs to their dendrites and use microtubule-based transport to increase this asymmetric localization following proteotoxic stress.
View Article and Find Full Text PDFInsights Into Retinal Pathologies in Neurological Disorders: A Focus on Parkinson's Disease, Multiple Sclerosis, Amyotrophic Lateral Sclerosis, and Alzheimer's Disease.
J Neurosci Res
January 2025
International School of Medicine, University of Health Sciences, Istanbul, Turkey.
Neurological diseases are central nervous system (CNS) disorders affecting the whole body. Early diagnosis of the diseases is difficult due to the lack of disease-specific tests. Adding new biomarkers external to the CNS facilitates the diagnosis of neurological diseases.
View Article and Find Full Text PDFRelease of FUS into the extracellular space is regulated by its amino-terminal prion-like domain.
FEBS Lett
December 2024
School of Pharmacy at Fukuoka, International University of Health and Welfare, Fukuoka, Japan.
Fused in sarcoma (FUS) is a causative factor of amyotrophic lateral sclerosis (ALS) and is believed to propagate pathologically by transmission from cell to cell. However, the mechanism underlying FUS release from cells, which is a critical step for the propagation system, remains poorly understood. This study conducted an analysis of the release of human and mouse FUS from neurons, revealing that human FUS is significantly released into the media compared to its mouse counterpart.
View Article and Find Full Text PDFDecoding TDP-43: the molecular chameleon of neurodegenerative diseases.
Acta Neuropathol Commun
December 2024
Shenzhen Baoan Traditional Chinese Medicine Hospital, Guangzhou University of Chinese Medicine, Shenzhen, Guang Dong, 518000, China.
TAR DNA-binding protein 43 (TDP-43) has emerged as a critical player in neurodegenerative disorders, with its dysfunction implicated in a wide spectrum of diseases including amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration (FTLD), and Alzheimer's disease (AD). This comprehensive review explores the multifaceted roles of TDP-43 in both physiological and pathological contexts. We delve into TDP-43's crucial functions in RNA metabolism, including splicing regulation, mRNA stability, and miRNA biogenesis.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!