Dysregulation of protein phosphatase 2A in parkinson disease and dementia with lewy bodies. Author Hye-Jin Park, Kang-Woo Lee, Eun Park, Stephanie Oh, Run Yan, Jie Zhang, Thomas Beach, Charles Adler, Michael Voronkov, Steven Braithwaite, Jeffry Stock, M Maral Mouradian Publication Year 2016 Type Journal Article Abstract OBJECTIVE: Protein phosphatase 2A (PP2A) is a heterotrimeric holoenzyme composed of a catalytic C subunit, a structural A subunit, and one of several regulatory B subunits that confer substrate specificity. The assembly and activity of PP2A are regulated by reversible methylation of the C subunit. -Synuclein, which aggregates in Parkinson disease (PD) and dementia with Lewy bodies (DLB), is phosphorylated at Ser, and PP2A containing a B55 subunit is a major phospho-Ser phosphatase. The objective of this study was to investigate PP2A in -synucleinopathies.METHODS: We compared the state of PP2A methylation, as well as the expression of its methylating enzyme, leucine carboxyl methyltransferase (LCMT-1), and demethylating enzyme, protein phosphatase methylesterase (PME-1), in postmortem brains from PD and DLB cases as well as age-matched Controls. Immunohistochemical studies and quantitative image analysis were employed.RESULTS: LCMT-1 was significantly reduced in the substantia nigra (SN) and frontal cortex in both PD and DLB. PME-1, on the other hand, was elevated in the PD SN. In concert with these changes, the ratio of methylated PP2A to demethylated PP2A was markedly decreased in PD and DLB brains in both SN and frontal cortex. No changes in total PP2A or total B55 subunit were detected.INTERPRETATION: These findings support the hypothesis that PP2A dysregulation in -synucleinopathies may contribute to the accumulation of hyperphosphorylated -synuclein and to the disease process, raising the possibility that pharmacological means to enhance PP2A phosphatase activity may be a useful disease-modifying therapeutic approach. Journal Ann Clin Transl Neurol Volume 3 Issue 10 Pages 769-780 Date Published 2016 Oct ISSN Number 2328-9503 DOI 10.1002/acn3.337 Alternate Journal Ann Clin Transl Neurol PMCID PMC5048387 PMID 27752512 PubMedPubMed CentralGoogle ScholarBibTeXEndNote X3 XML