p38 MAPK and PI3K/AKT signalling cascades in Parkinson's disease

Parkinson''s disease (PD) is a chronic neurodegenerative condition which has the second largest incidence rate among all other neurodegenerative disorders barring Alzheimer''s disease (AD). Currently there is no cure and researchers continue to probe the therapeutic prospect in cell cultures and animal models of PD. Out of several factors contributing to PD prognosis, the role of p38 MAPKs (mitogen-activated protein (MAP) kinase) and PI3K/AKT signalling module in PD brains is crucial because impaired balance between the pro-apoptotic and anti-apoptotic pathways trigger unwanted phenotypes such as microglia activation, neuroinflammation, oxidative stress, and apoptosis. These factors continue challenging the brain homeostasis in initial stages thereby essentially assisting the dopaminergic (DA) neurons towards progressive degeneration in PD. Neurotherapeutics against PD shall then be targeted against the misregulated accomplices of the p38 and PI3K/AKT cascades. In this review, we have outlined many such established mechanism involving the p38 MAPK and PI3K/AKT pathways which can offer therapeutic windows for rectification of aberrant DA neuronal dynamics in PD brains.