The Ubiquitin Proteasome System and Cerebellar Developmental Disease

  • Jerry VriendEmail author
  • Xiaodan Jiao
Part of the Contemporary Clinical Neuroscience book series (CCNE)


A variety of developmental diseases of the cerebellum are associated with dysregulation of proteins regulated by the ubiquitin proteasome system (UPS). Dysfunction of the UPS is observed in several types of spinocerebellar ataxias associated with polyglutamine accumulation. Spinocerebellar ataxia type 3 is caused by a genetic defect ion the Atxn3 gene, which codes for a deubiquitinase enzyme. Defects in expression of a variety of ubiquitin ligases are associated with Friedreich’s ataxia, ataxia-telangiectasia, and cerebellar hemangioblastoma. Mutations in a number of genes for ubiquitin ligases are risk factors for autism. Subtypes of medulloblastoma are associated with specific defects in proteasome subunits and with deficiencies in components of the APC/C ubiquitin ligase complex regulating the cell cycle. Targeting various components of the UPS system may contribute to a future therapeutic approach which restores protein homeostasis in various cerebellar diseases.



Atrophin-interacting protein


Ataxin-1 ubiquitin-like interacting protein


Anaphase-promoting complex/cyclosome


Autism spectrum disorder




Ataxia-telangiectasia mutated


Ataxin 1


Ataxin 3


Cytosine-adenine-guanine repeat


Checkpoint with forkhead and ring finger domains


Dentatorubropallidoluysian atrophy




Ubiquitin-conjugating enzyme


Ubiquitin ligase


Ubiquitin-activating enzyme


Friedreich’s ataxia




Hypoxia-inducible factor 1


Inositol triphosphate receptor isoform




Machado-Joseph disease


Ring finger protein


Spinocerebellar ataxia


Ubiquitin protein ligase E3 component N-recognin 4


Ubiquitin proteasome system


Ubiquitin-specific protease


Vascular endothelial growth factor


von Hippel-Lindau protein


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Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  1. 1.Department of Human Anatomy and Cell Science, Max Rady College of Medicine, Rady Faculty of Health SciencesUniversity of ManitobaWinnipegCanada

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