Mitochondrial Deficiencies and Oxidative Stress in Parkinson’s Disease: A Slippery Slope to Cell Death

Parkinson’s disease (PD) affects over 500,000 Americans. Most cases of PD are idiopathic, or occurring without a known cause. Two pathological features of PD, α-synuclein-rich Lewy bodies (LB) and oxidative damage, hint at the cause of the disease. Yet, disparities in recessive forms of PD increase the complexity of the disease mechanism. These recessive forms occur earlier in life and are devoid of LB. One common feature among these forms is the extensive presence of reactive oxygen species (ROS). Studies with the toxin MPTP produced similar pathologies to recessive PD but intriguingly showed inhibition of complex I in the mitochondria. These and other studies chased the mitochondria as the progenitor of oxidative stress. These investigations also uncovered several disparate mitochondrial proteins, one of which is a Kreb’s cycle enzyme, α-ketoglutarate dehydrogenase (α-KGDH). Interestingly, α-KGDH activity is reduced in both Alzheimer’s disease (AD) and PD. Links to both diseases may be due to its role in the inactivation of complex I. This review will focus on how mitochondrial impairments enhance neuronal toxicity in PD.