Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

Kinases and Their Potential as Therapeutic Targets in Huntington’s Disease

Version 1 : Received: 30 June 2022 / Approved: 1 July 2022 / Online: 1 July 2022 (17:47:10 CEST)

A peer-reviewed article of this Preprint also exists.

White, A.; McGlone, A.; Gomez-Pastor, R. Protein Kinase CK2 and Its Potential Role as a Therapeutic Target in Huntington’s Disease. Biomedicines 2022, 10, 1979. White, A.; McGlone, A.; Gomez-Pastor, R. Protein Kinase CK2 and Its Potential Role as a Therapeutic Target in Huntington’s Disease. Biomedicines 2022, 10, 1979.

Journal reference: Biomedicines 2022, 10, 1979
DOI: 10.3390/biomedicines10081979

Abstract

Huntington’s Disease (HD) is a devastating neurodegenerative disorder caused by a CAG trinucleotide repeat expansion in the HTT gene, for which no disease modifying therapies are currently available. Much of the recent research has focused on developing therapies to directly lower HTT expression, and while promising, these therapies have presented several challenges regarding administration and efficacy. Another promising therapeutic approach is the modulation of HTT post-translational modifications (PTMs) that are dysregulated in disease and have shown to play a key role in HTT toxicity. Among all PTMs, modulation of HTT phosphorylation has been proposed as an attractive therapeutic option due to the possibility of orally administering specific kinase effectors. One of the kinases described to participate in HTT phosphorylation is Protein Kinase CK2. CK2 has recently emerged as a target for the treatment of several neurological and psychiatric disorders, although its role in HD remains controversial. While pharmacological studies in vitro inhibiting CK2 resulted in reduced HTT phosphorylation and increased toxicity, genetic approaches in mouse models of HD have provided beneficial effects. In this review we discuss potential therapeutic approaches related to the manipulation of HTT-PTMs with special emphasis on the role of CK2 as a therapeutic target in HD.

Keywords

post-translation modifications; CK2; Huntington’s Disease; Kinase Inhibition; HTT phosphorylation

Subject

LIFE SCIENCES, Molecular Biology

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