Results
Title

Altered Protein Palmitoylation as Disease Mechanism in Neurodegenerative Disorders.

Authors

Wlodarczyk, Jakub; Bhattacharyya, Raja; Dore, Kim; Ho, Gary P. H.; Martin, Dale D. O.; Mejias, Rebeca; Hochrainer, Karin

Abstract

Palmitoylation, a lipid-based posttranslational protein modification, plays a crucial role in regulating various aspects of neuronal function through altering protein membrane-targeting, stabilities, and protein–protein interaction profiles. Disruption of palmitoylation has recently garnered attention as disease mechanism in neurodegeneration. Many proteins implicated in neurodegenerative diseases and associated neuronal dysfunction, including but not limited to amyloid precursor protein, β-secretase (BACE1), postsynaptic density protein 95, Fyn, synaptotagmin-11, mutant huntingtin, and mutant superoxide dismutase 1, undergo palmitoylation, and recent evidence suggests that altered palmitoylation contributes to the pathological characteristics of these proteins and associated disruption of cellular processes. In addition, dysfunction of enzymes that catalyze palmitoylation and depalmitoylation has been connected to the development of neurological disorders. This review highlights some of the latest advances in our understanding of palmitoylation regulation in neurodegenerative diseases and explores potential therapeutic implications.

Subjects

POST-translational modification; POSTSYNAPTIC density protein; AMYLOID beta-protein precursor; PALMITOYLATION; SUPEROXIDE dismutase; HUNTINGTIN protein

Publication

Journal of Neuroscience, 2024, Vol 44, Issue 40, p1

ISSN

0270-6474

Publication type

Academic Journal

DOI

10.1523/JNEUROSCI.1225-24.2024