The Role of Caspases in Parkinson’s Disease Pathogenesis: A Brief Look at the Mitochondrial Pathway

Mitochondrial dysfunction plays a vital role in the progression of Parkinson’s Disease (PD) via inducing activation of Caspases and Caspase cascade. This review focuses on the mitochondrial intrinsic pathway involved in Caspase activation and its participation in PD progression. Oxidative stress, ER stress, environmental toxins, alongside genetic mutations and excitotoxicity can stimulate activation of different pathways including inflammatory, JNK, NFκB and p38 leading to mitochondrial dysfunction and the release of cytochrome C. Subsequently, this leads to the activation of initiator Caspases (-2, -8, -9 and -10), followed by the activation of executioner Caspases (-3, -6 and -7), resulting in dopaminergic cell death and development of PD. This review summarises and updates the most recent findings related to the activation of specific Caspases via different routes focusing on the mitochondrial intrinsic pathway that leads to the destruction of dopaminergic neurons resulting in PD pathogenesis.