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Review
. 2022 Mar 24:16:818757.
doi: 10.3389/fnins.2022.818757. eCollection 2022.

The Molecular Basis of Spinocerebellar Ataxia Type 7

Rituparna Goswami  1 , Abudu I Bello  1 , Joe Bean  1 , Kara M Costanzo  1 , Bwaar Omer  1 , Dayanne Cornelio-Parra  1 , Revan Odah  1 , Amit Ahluwalia  1 , Shefaa K Allan  1 , Nghi Nguyen  1 , Taylor Shores  1 , N Ahmad Aziz  2 , Ryan D Mohan  1
Affiliations
Review

The Molecular Basis of Spinocerebellar Ataxia Type 7

Rituparna Goswami et al. Front Neurosci. .

Abstract

Spinocerebellar ataxia (SCA) type 7 (SCA7) is caused by a CAG trinucleotide repeat expansion in the ataxin 7 (ATXN7) gene, which results in polyglutamine expansion at the amino terminus of the ATXN7 protein. Although ATXN7 is expressed widely, the best characterized symptoms of SCA7 are remarkably tissue specific, including blindness and degeneration of the brain and spinal cord. While it is well established that ATXN7 functions as a subunit of the Spt Ada Gcn5 acetyltransferase (SAGA) chromatin modifying complex, the mechanisms underlying SCA7 remain elusive. Here, we review the symptoms of SCA7 and examine functions of ATXN7 that may provide further insights into its pathogenesis. We also examine phenotypes associated with polyglutamine expanded ATXN7 that are not considered symptoms of SCA7.

Keywords: ATXN7; SAGA complex; USP22; deubiquitination; polyglutamine expansion.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Macular degeneration is a unique feature of SCA7. (Left) A healthy macula (the portion of the retina representing the center of the visual field, which has the highest visual acuity). Adapted from Stanford Medicine, Fundoscopic Exam. (Right) Extreme macular degeneration in late-stage SCA7. Adapted from La Spada, Spinocerebellar Ataxia Type 7.
FIGURE 2
FIGURE 2
Age of SCA7 onset vs. ATXN7 CAG repeat size. The symbol ∙ indicates values outside the range (outliers). Adapted from Michalik et al. (2004), Spinocerebellar ataxia type 7 associated with pigmentary retinal dystrophy.
See this image and copyright information in PMC

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