The mouse ALS gene spans at least 6 kb. It contains 2 exons which encode a protein highly homologous to human and rat ALS. It was localized to mouse chromosome 17 by flourescent in situ hybridization. The 5' flanking region lacks a TATA box but contains GC boxes that may be recognised by transcription factors such as Spl. Hepatic ALS mRNA is decreased in rats following hypophysectomy, and restored by stimulated ALS promoter activity in a rat hepatoma cell line, but not in 3T3-F442A mouse preadipocyte fibroblasts, suggesting that utilisation of the ALS promoter is cell-type specific. The rat hepatoma system is a promising system to study the regulation of ALS gene expression, and the signalling pathways of CH regulation.
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http://dx.doi.org/10.1016/0955-2235(95)00024-0 | DOI Listing |
J Neural Transm (Vienna)
January 2025
Neurology Department, LR18SP03, Razi University Hospital, Tunis, Tunisia.
Amyotrophic Lateral Sclerosis(ALS) has traditionally been managed as a neuromuscular disorder. However, recent evidence suggests involvement of non-motor domains. This study aims to evaluate the impact of APOE and MAPT genotypes on the cognitive features of ALS.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Amsterdam UMC, Amsterdam, Netherlands.
Background: The TMEM106B protein is critical for proper functioning of the endolysomal system, which is utilised by all cells to traffic and degrade molecular cargo. Genome-wide association studies identified a haplotype in the TMEM106B gene that is associated with increased risk for Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), and frontotemporal lobar degeneration with TAR DNA binding protein inclusions (FTLD-TDP). However, the causal variant that drives the association has thus far remained elusive.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Background: Emerging evidence support the notion that loss of splicing repression by TDP-43, an RNA binding protein that was first implicated in ALS-FTD, underlies their pathogenesis. Previously, we showed that delivery of an AAV9 vector at early postnatal day expressing a fusion protein, termed CTR comprised of the N-terminal region of TDP-43 and an unrelated splicing repressor termed RAVER1 complemented the loss of TDP-43 in mice lacking TDP-43 in spinal motor neurons (ChAT-IRES-Cre;tardbp mice). To translate this potential therapeutic strategy to the clinic, it will be important to demonstrate benefit of such AAV delivery of CTR to motor neurons in adult mice.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Barrow Neurological Institute, Phoenix, AZ, USA; Arizona State University, Tempe, AZ, USA.
Background: TDP-43 is an RNA binding protein that is a pathological hallmark of multiple neurodegenerative diseases including Amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and Alzheimer's disease (AD). The frequency of observed TDP-43 pathology is estimated at 97% in ALS, 45% in FTD and 40-57% in AD and is characterized by a mislocalization of TDP-43 from the nucleus to the cytoplasm. Indeed, TDP-43 is the third most common proteinopathy in AD, behind only Amyloid beta and Tau.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Department of Neurology, Columbia University, New York, NY, USA.
Background: Lipid dysregulation is a known feature of Alzheimer's Disease. Importantly, alterations in lipids pathways affect immune responses in cells like microglia, which have been shown to accumulate cholesterol in both aging and neurodegeneration. Recently, the presence of TDP-43 inclusions has been linked to increased severity of cognitive impairment in AD patients.
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