SIRT2-mediated protein deacetylation: An emerging key regulator in brain physiology and pathology.
Protein function is considerably altered by posttranslational modification. In recent years, cycles of acetylation/deacetylation emerged as fundamental regulators adjusting biological activity of many proteins. Particularly, protein deacetylation by Sirtuins, a family of atypical histone deacetylases (HDACs), was demonstrated to regulate fundamental cell biological processes including gene expression, genome stability, mitosis, nutrient metabolism, aging, mitochondrial function and cell motility. Given this wealth of biological functions, perhaps not unexpectedly then, pharmacological compounds targeting Sirtuin activity are now prime therapeutic agents for alleviating severity of major diseases encompassing diabetes, cancer, cardiovascular and neurodegenerative disorders in many organs. In this review, we will focus on the brain and its physiological and pathological processes governed by Sirtuin-mediated deacetylation. Besides discussing Sirtuin function in neurodegenerative diseases, emphasis will be given on the mounting evidence deciphering key developmental brain functions for Sirtuins in neuronal motility, neuroprotection and oligodendrocyte differentiation. In this respect, we will particularly highlight functions of the unconventional family member SIRT2 in post-mitotic neurons and glial cells.
Harting
Kai
K
Neuronal Gene Expression Laboratory, Department of Molecular Biology, Interfaculty Institute for Cell Biology, Eberhard-Karls-University Tübingen, Auf der Morgenstelle 15, 72076 Tübingen, Germany.
Knöll
Bernd
B
D000107:Acetylation; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001921:Brain / Q000473:pathology / Q000502:physiology / Q000503:physiopathology; D031204:Caloric Restriction; D002453:Cell Cycle / Q000502:physiology; D002465:Cell Movement; D049109:Cell Proliferation; D043171:Chromosomal Instability; D019970:Cocaine-Related Disorders; D005786:Gene Expression Regulation; D005910:Glioma / Q000378:metabolism; D006801:Humans; D019636:Neurodegenerative Diseases / Q000473:pathology / Q000503:physiopathology; D009474:Neurons / Q000166:cytology / Q000502:physiology; D011499:Protein Processing, Post-Translational; D056565:Sirtuin 2 / Q000235:genetics / Q000378:metabolism*
D056565:Sirtuin 2