Therapeutic Strategies for Spinocerebellar Ataxia Type 1

Abstract

Spinocerebellar ataxia type 1 (SCA1) is an autosomal dominant neurodegenerative disorder that affects one or two individuals per 100,000. The disease is caused by an extended CAG repeat in exon 8 of the ATXN1 gene and is characterized mostly by a profound loss of cerebellar Purkinje cells, leading to disturbances in coordination, balance, and gait. At present, no curative treatment is available for SCA1. However, increasing knowledge on the cellular and molecular mechanisms of SCA1 has led the way towards several therapeutic strategies that can potentially slow disease progression. SCA1 therapeutics can be classified as genetic, pharmacological, and cell replacement therapies. These different therapeutic strategies target either the (mutant) ATXN1 RNA or the ataxin-1 protein, pathways that play an important role in downstream SCA1 disease mechanisms or which help restore cells that are lost due to SCA1 pathology. In this review, we will provide a summary of the different therapeutic strategies that are currently being investigated for SCA1.

Differential microRNA expression in the SH-SY5Y human cell model as potential biomarkers for Huntington’s disease

“… Chen D. et al (2022) also found that miR-504-3p was differentially upregulated in hTau mice. We found that miR-504-3p can target the ATXN1 gene, which has been extensively studied in NDs ( Kerkhof et al, 2023 ). Statistical analysis of relative expression results shows that ATXN1 gene expression was significantly downregulated ( p < 0.01) in Q74 ( Figure 4B ).…”