Let's get fat: emergence of S-acylation as a therapeutic target in Huntington disease.
Biochem Soc Trans
; 52(3): 1385-1392, 2024 Jun 26.
Article
in En
| MEDLINE
| ID: mdl-38695682
ABSTRACT
Protein mislocalization is a key initial step in neurodegeneration, regardless of etiology, and has been linked to changes in the dynamic addition of saturated fatty acids to proteins, a process known as S-acylation. With the advent of new techniques to study S-acylation and the recent discovery of new enzymes that facilitate protein deacylation, novel small molecules are emerging as potential new therapeutic treatments. Huntington disease (HD) is a devastating, fatal neurodegenerative disease characterized by motor, cognitive, and psychiatric deficits caused by a CAG repeat expansion in the HTT gene. The protein that is mutated in HD, huntingtin, is less S-acylated which is associated with mutant HTT aggregation and cytotoxicity. Recent exciting findings indicate that restoring S-acylation in HD models using small molecule inhibitors of the deacylation enzymes is protective. Herein, we set out to describe the known roles of S-acylation in HD and how it can be targeted for therapeutic design.
Key words
Full text:
1
Database:
MEDLINE
Main subject:
Huntington Disease
/
Huntingtin Protein
Limits:
Animals
/
Humans
Language:
En
Journal:
Biochem Soc Trans
Year:
2024
Type:
Article
Affiliation country:
Canada