CHAPTER 7: Protein Phosphatases in Parkinson’s Disease Check Access

Phosphorylation and dephosphorylation are among the key mechanisms underlying the pathogenesis of Parkinson's disease (PD). Accumulating genetic evidence implicates the dysfunction of several kinases and phosphatases, as well as the upstream regulatory proteins and the downstream targets. So far, there is direct evidence for the involvement of at least six tyrosine phosphatases (RPTPβ/ζ, PTP-PEST, STEP, SHP-2, tyrosine and lipid phosphatase PTEN, and the dual-specificity phosphatase DUSP1), and for the involvement of at least four serine/threonine phosphatases (PP1, PP2A, PP3/calcineurin, and PHLPP1). The critical dephosphorylation mechanisms provide number of potential targets for drug discovery. Modulation of the activity of protein phosphatases or of other members of their signaling pathways has the potential to serve as the next generation of PD therapeutic targets.