Spinocerebellar ataxias (SCAs) are a group of heterogeneous autosomal dominant neurodegenerative diseases characterized by loss of balance and coordination. Most SCAs feature pronounced Purkinje cell loss and cerebellar atrophy, while other regions such as the spinal cord, basal ganglia, and brainstem nuclei (including the pons) may also be affected. As no treatments currently exist to slow or halt disease progression, advancing research into SCA pathobiology and therapeutic targets remains a critical priority. This chapter surveys the current toolbox of SCA models, including patient-derived induced pluripotent stem cells (iPSCs), cerebellar organoids, rodents, zebrafish, Drosophila and C. elegans models. For each model, we summarize major pathological, biochemical, electrophysiological, and behavioral phenotypes. Together, these models provide complementary windows into SCA biology and an increasingly robust foundation for therapeutic discovery.

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Models of Spinocerebellar Ataxias

  • Daniel R. Scoles,
  • Stepan Kapl,
  • Nilpawan Roy Choudhury,
  • Stefan M. Pulst,
  • Mandi Gandelman

摘要

Spinocerebellar ataxias (SCAs) are a group of heterogeneous autosomal dominant neurodegenerative diseases characterized by loss of balance and coordination. Most SCAs feature pronounced Purkinje cell loss and cerebellar atrophy, while other regions such as the spinal cord, basal ganglia, and brainstem nuclei (including the pons) may also be affected. As no treatments currently exist to slow or halt disease progression, advancing research into SCA pathobiology and therapeutic targets remains a critical priority. This chapter surveys the current toolbox of SCA models, including patient-derived induced pluripotent stem cells (iPSCs), cerebellar organoids, rodents, zebrafish, Drosophila and C. elegans models. For each model, we summarize major pathological, biochemical, electrophysiological, and behavioral phenotypes. Together, these models provide complementary windows into SCA biology and an increasingly robust foundation for therapeutic discovery.