Programmed Cell Death in Parkinson's Disease

Parkinson's disease is a debilitating disorder characterized by a progressive loss of dopaminergic neurons caused by programmed cell death. The aim of this review is to provide an up-to-date summary of the major programmed cell death pathways as they relate to PD. For a long time, programmed cell death has been synonymous with apoptosis but there now is evidence that other types of programmed cell death exist, such as autophagic cell death or programmed necrosis, and that these types of cell death are relevant to PD. The pathways and signals covered here include namely the death receptors, BCL-2 family, caspases, calpains, cdk5, p53, PARP-1, autophagy, mitophagy, mitochondrial fragmentation, and parthanatos. The review will present evidence from postmortem PD studies, toxin-induced models (especially MPTP/MPP+, 6-hydroxydopamine and rotenone), and from alpha-synuclein, LRRK2, Parkin, DJ-1, and PINK1 genetic models of PD, both in vitro and in vivo.