Fig. (1).

Neurotoxins like MPTP and mutation in mitochondrial genes cause mitochondrial dysfunction. Multiple intermediate events like decrease in ATP production, neuronal depolarization and excitotoxicity, oxidative stress and failure of ubiquitin-proteasomal system all converge to apoptosis. Aggregation of toxic α-synuclein may cause mitochondrial dysfunction and vice versa. Further, aggregated α-synuclein may activate microglia which can lead to neuroinflammation and subsequently demise of the neurons. Neuronal death may ultimately lead to motor and non-motor deficits in PD.