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The Ubiquitin Proteasome System and Cerebellar Developmental Disease

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Book cover Development of the Cerebellum from Molecular Aspects to Diseases

Part of the book series: Contemporary Clinical Neuroscience ((CCNE))

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Abstract

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.

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Abbreviations

AIP:

Atrophin-interacting protein

A1UP:

Ataxin-1 ubiquitin-like interacting protein

APC/C:

Anaphase-promoting complex/cyclosome

ASD:

Autism spectrum disorder

AT:

Ataxia-telangiectasia

ATM:

Ataxia-telangiectasia mutated

ATXN1:

Ataxin 1

ATXN3:

Ataxin 3

CAG:

Cytosine-adenine-guanine repeat

CHFR:

Checkpoint with forkhead and ring finger domains

DRPLA:

Dentatorubropallidoluysian atrophy

DUB:

Deubiquitinase

E2:

Ubiquitin-conjugating enzyme

E3:

Ubiquitin ligase

E1:

Ubiquitin-activating enzyme

FRDA:

Friedreich’s ataxia

FXN:

Frataxin

HIF-1:

Hypoxia-inducible factor 1

ITPR:

Inositol triphosphate receptor isoform

MB:

Medulloblastoma

MJD:

Machado-Joseph disease

RNF:

Ring finger protein

SCA:

Spinocerebellar ataxia

UBR:

Ubiquitin protein ligase E3 component N-recognin 4

UPS:

Ubiquitin proteasome system

USP:

Ubiquitin-specific protease

VEGF:

Vascular endothelial growth factor

VHL:

von Hippel-Lindau protein

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  1. Department of Human Anatomy and Cell Science, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada

    Jerry Vriend & Xiaodan Jiao

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  1. Jerry Vriend
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  2. Xiaodan Jiao
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Correspondence to Jerry Vriend .

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  1. Department of Human Anatomy and Cell Science, The Children’s Hospital Research Institute of Manitoba (CHRIM), Max Rady College of Medicine, Rady Faculty of Health Science, University of Manitoba, Winnipeg, MB, Canada

    Hassan Marzban

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Vriend, J., Jiao, X. (2017). The Ubiquitin Proteasome System and Cerebellar Developmental Disease. In: Marzban, H. (eds) Development of the Cerebellum from Molecular Aspects to Diseases. Contemporary Clinical Neuroscience. Springer, Cham. https://doi.org/10.1007/978-3-319-59749-2_9

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