Protein Phosphatase 2A: a Double-Faced Phosphatase of Cellular System and Its Role in Neurodegenerative Disorders

Protein phosphatase 2A (PP2A), a ubiquitously expressed serine/threonine phosphatase, is a vitally important phosphatase for the cellular system. Structurally, it is constituted of three different subunits, namely catalytic subunit (PP2Ac), structural scaffold subunit (PP2A-A), and regulatory subunit (PP2A-B). All subunits have various isoforms, and catalytic and scaffold subunits are ubiquitously expressed, whereas regulatory subunits are more specific to tissue and cell type. It is the numerous possibilities of PP2A holoenzyme assembly with varying isoform components that make it possess a dual nature of activator or the inhibitory character in different signaling pathways, namely neural developmental pathways, Akt/protein kinase B pathway, NF-kB pathway, MAPK pathway, apoptosis pathway, and cell cycle progression to name a few. Importantly, the expression of PP2A in the brain is highest among the serine phosphatases and is known to actively participate in the neural development process. However, the exact mechanism of action of PP2A is still debated and enunciating the holoenzyme components, especially the regulatory subunit of PP2A involved in regulating neural developmental process is still poorly understood. In this review, we try to throw some light on the involvement of various PP2A holoenzyme forms in the process of neurogenesis and progression of neurodegenerative diseases.