Implications of p53 in mitochondrial dysfunction and Parkinson's disease

Purpose: To study the underlying molecular mechanisms of p53 in the mitochondrial dysfunction and the pathogenesis of Parkinson's disease (PD), and provide a potential therapeutic target for PD treatment.

Methods: We review the contributions of p53 to mitochondrial changes leading to apoptosis and the subsequent degeneration of dopaminergic neurons in PD.

Results: P53 is a multifunctional protein implicated in the regulation of diverse cellular processes via transcription-dependent and transcription-independent mechanisms. Mitochondria are vital subcellular organelles for that maintain cellular function, and mitochondrial defect and impairment are primary causes of dopaminergic neuron degeneration in PD. Increasing evidence has revealed that mitochondrial dysfunction-associated dopaminergic neuron degeneration is tightly regulated by p53 in PD pathogenesis. Neurodegenerative stress triggers p53 activation, which induces mitochondrial changes, including transmembrane permeability, reactive oxygen species production, Ca2+ overload, electron transport chain defects and other dynamic alterations, and these changes contribute to neurodegeneration and are linked closely with PD occurrence and development. P53 inhibition has been shown to attenuate mitochondrial dysfunction and protect dopaminergic neurons from degeneration under conditions of neurodegenerative stress.

Conclusions: p53 appears to be a potential target for neuroprotective therapy of PD.