Roles of PI3K/AKT/PTEN pathway in the pathogenesis of parkinson’s disease and the neuropsychiatric symptoms.

ABSTRACT

Parkinson's disease is a neurodegenerative disorder associated with loss of dopaminergic neurons in substantianigra caused by severe neuro-degeneration, which is the second most common neurodegenerative disorder after Alzheimer’s disease.Parkinson's disease has a high prevalence of psychiatric comorbidity including depression. The neuropsychiatric symptoms are common in Parkinson's disease and may precede onset of motor symptoms. Increasing interest is often addressed to the selective targeting of some of metabotropic glutamate receptors that inhibit the transmitter release at synapses in the basal ganglia. The metabotropic glutamate receptors may be coupled to the phosphatidylinositol-3-kinase (PI3K), AKT, and PTEN pathways, whichplay a central role in cell survival. A better understanding of the molecular connections in the PI3K pathways could uncover new targets for drug development in Parkinson's disease.