Topic: SCA2

Polyglutamine Spinocerebellar ataxias (SCA) are a group of genetic disorders caused by an expansion of the CAG trinucleotide in their causative genes. Currently, there is limited understanding of the underlying molecular pathogenesis alterations. Activity-induced inhibitor of death genes (AID) is a group of pro-survival genes that have been found to be neuroprotective in several neurological disorders. In this project, our goal is to explore the potential of modulating AID expression to mitigate disease progression in models of SCA2 and SCA3, the most prevalent ataxias worldwide. Our findings

Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominant disorder caused by an abnormal expansion of the trinucleotide CAG in the coding region of the ATXN2 gene. This is translated into an expanded polyglutamine tract in the ataxin-2 protein, leading to a gain of toxic function affecting especially the neurons. Besides the pathogenic mechanisms triggered by ataxin-2 dysfunction, previous studies showed that abnormally expanded CAG repeats display toxicity already at the RNA level, contributing to disease pathogenesis. Considering these data, it is important to develop therapeutic approac

Spinocerebellar ataxia type 2 (SCA2) is a rare neurodegenerative disorder characterized by cerebellar dysfunction and significant loss of Purkinje cells, with subsequent involvement of other brain regions, suggesting a potential disease-spreading mechanism. Our study sheds light on SCA2 pathogenesis by revealing the presence of mutant ATXN2 mRNA within small extracellular vesicles (sEVs). These sEVs demonstrate the ability to transport the mutant mRNA to recipient cells, leading to its translation and the formation of mutant protein aggregates, a neuropathological hallmark of SCA2.Additionally

Spinocerebellar ataxias (SCA) are a group of inherited neurodegenerative diseases. The most common SCAs are caused by an expansion of the trinucleotide CAG, which produces a polyglutamine tract in their encoded proteins, leading to their aggregation. Patients suffering from these disorders display movement impairments, and no effective treatment exists, leading to death 10-15 years after disease onset. Until now, nearly all attempts to use traditional N-methyl-d-aspartate receptor (NMDAR) antagonists to treat neurodegenerative diseases have failed. This is because NMDARs are not only promoters

Spinocerebellar ataxia type 2 (SCA2) is a rare neurodegenerative disease that arises from a mutation within the ATXN2 gene characterised by abnormally long CAG trinucleotide repeats. The mutant gene product is the ataxin-2 protein, which bears an expanded glutamine tract. The mutant protein is known to disrupt molecular pathways within cells, leading to cellular death and neurodegeneration within specific brain regions.To cope with disrupted pathways, cells have mechanisms such as the Integrated Stress Response (IRS), which help cells resolve stress situations by reorganising translation to pr