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. 2020 Sep 29;21(19):7182. doi: 10.3390/ijms21197182

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© 2020 by the authors.

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).

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Effects of MPTP/MPP⁺ on acetylation of nonhistone proteins. MPTP/MPP+ inhibits SIRT1 expression or activity to block deacetylation of various substrates, such as p53, p65, PGC-1α, and LC3, which leads to neuronal apoptosis, neuroinflammatory activation, mitochondrial dysfunction, and autophagy inhibition, respectively. However, MPTP/MPP+ also promotes GCN5 expression to increase PGC-1α acetylation. In addition, MPTP/MPP⁺ activates SIRT2 to induce deacetylation of Foxo3a, enhancing Bim transcription and thus leading to neurodegeneration.