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Review
. 2022 Feb 5;11(3):556.
doi: 10.3390/cells11030556.

Deubiquitinases in Neurodegeneration

Abudu I Bello  1 , Rituparna Goswami  1 , Shelby L Brown  1 , Kara Costanzo  1 , Taylor Shores  1 , Shefaa Allan  1 , Revan Odah  1 , Ryan D Mohan  1
Affiliations
Review

Deubiquitinases in Neurodegeneration

Abudu I Bello et al. Cells. .

Abstract

Ubiquitination refers to the conjugation of the ubiquitin protein (a small protein highly conserved among eukaryotes) to itself or to other proteins through differential use of ubiquitin's seven internal linkage sites or the amino-terminal amino group. By creating different chain lengths, an enormous proteomic diversity may be formed. This creates a signaling system that is central to controlling almost every conceivable protein function, from proteostasis to regulating enzyme function and everything in between. Protein ubiquitination is reversed through the activity of deubiquitinases (DUBs), enzymes that function to deconjugate ubiquitin from itself and protein substrates. DUBs are regulated through several mechanisms, from controlled subcellular localization within cells to developmental and tissue specific expression. Misregulation of DUBs has been implicated in several diseases including cancer and neurodegeneration. Here we present a brief overview of the role of DUBs in neurodegeneration, and as potential therapeutic targets.

Keywords: Drosophila; deubiquitinase; neurodegeneration; ubiquitin; ubiquitin-specific protease.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the writing of the manuscript, or in the decision to publish the review.

Figures

Figure 1
Figure 1
Mechanism of DUB involvement in neurodegeneration. This figure shows three mechanisms of dysfunction in DUBs: (1) direct mutations in the gene encoding the DUB; (2) a central role for the DUB in a ubiquitin-dependent quality control pathway implicated in disease; and (3) involvement of the DUB in handling a specific substrate that is critical to neurodegenerative disorders.
Figure 2
Figure 2
Deubiquitinases implicated in neurodegenerative diseases and associated pathways.
See this image and copyright information in PMC

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