A comprehensive review of iPS cell line-based disease modelling of the polyglutamine spinocerebellar ataxias 2 and 3: a focus on the research outcomes

Abstract

Spinocerebellar ataxia (SCAs) are a rare autosomal dominant neurodegenerative disorder. To date, approximately 50 different subtypes of SCAs have been characterized. The prevalent types of SCAs are usually of PolyQ origin, wherein the disease pathology is a consequence of multiple glutamine residues being encoded onto the disease proteins, causing expansions. SCAs 2 and 3 are the most frequently diagnosed subtypes, wherein affected patients exhibit certain characteristic physiological manifestations, such as gait ataxia and dysarthria. Nevertheless, other clinical signs were exclusive to these subtypes. Recently, multiple molecular diagnostic methods have been developed to identify and characterize these subtypes. Despite these advancements, the molecular pathology of SCAs remains unknown. To further understand the mechanisms involved in neurodegenerative SCAs 2 and 3, patient-derived induced pluripotent stem cell-based modelling is a compelling avenue to pursue. We cover the present state of iPSC-based in vitro illness modelling of SCA subtypes 2 and 3 below, along with a list of cell lines created, and the relevance of research outcomes to personalized autologous therapy.