Abstract
Parkinson’s disease (PD) is one of the most common neurodegenerative disorders. The neuropathological features of PD are selective and progressive loss of dopaminergic neurons in the substantia nigra pars compacta, deficiencies in striatal dopamine levels, and the presence of intracellular Lewy bodies. Interactions among aging and genetic and environmental factors are considered to underlie the common etiology of PD, which involves multiple changes in cellular processes. Recent studies suggest that changes in lysine acetylation and deacetylation of many proteins, including histones and nonhistone proteins, might be tightly associated with PD pathogenesis. Here, we summarize the changes in lysine acetylation of both histones and nonhistone proteins, as well as the related lysine acetyltransferases (KATs) and lysine deacetylases (KDACs), in PD patients and various PD models. We discuss the potential roles and underlying mechanisms of these changes in PD and highlight that restoring the balance of lysine acetylation/deacetylation of histones and nonhistone proteins is critical for PD treatment. Finally, we discuss the advantages and disadvantages of different KAT/KDAC inhibitors or activators in the treatment of PD models and emphasize that SIRT1 and SIRT3 activators and SIRT2 inhibitors are the most promising effective therapeutics for PD.
Highlights
Parkinson’s disease (PD) is the second most common neurodegenerative disorder, affecting approximately 1% of the population over the age of 60 and, drastically, up to 5% of the population over 85 [1,2]
The pan-HDAC inhibitors trichostatin A (TSA) and hydroxamic acid (SAHA) do not inhibit MPP+-induced cell death, but valproate (VPA) exacerbates MPP+-induced cell death in vitro [47]. These results indicate that MPTP/MPP+ widely inhibits the expression of KDACs, and this inhibition may be accompanied by compensatory upregulation of individual HDACs under certain conditions
Increases NAD+ levels in mitochondria and protects mitochondria [133]. These findings suggest that NAD+ precursors are potential clinical drugs for PD treatment
Summary
Parkinson’s disease (PD) is the second most common neurodegenerative disorder, affecting approximately 1% of the population over the age of 60 and, drastically, up to 5% of the population over 85 [1,2]. Recent investigations have suggested that lysine acetylation and deacetylation of numerous proteins, including histones and nonhistone proteins, as well as acetylation of α-syn itself, might be tightly associated with the molecular events underlying PD pathogenesis. We discuss the potential roles and mechanisms of lysine acetylation and deacetylation of histones and nonhistone proteins as well as the changes in lysine acetyltransferases (KATs) and lysine deacetylases (KDACs) associated with PD pathogenesis. 2020, 21 acetylation and deacetylation of numerous proteins, including histones and nonhistone proteins, as well as acetylation of α-syn itself, might be tightly associated with the molecular events underlying PD pathogenesis. Scdi.e2a0c2e0t,y2l1a,t7io18n2 of histones and nonhistone proteins as well as the changes in lysine of 22 acetyltransferases (KATs) and lysine deacetylases (KDACs) associated with PD pathogenesis.
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