The PINK1/Parkin-dependent mitophagy pathway and its role in Parkinson’s disease

Abstract

Parkinson's disease is the second most prevalent neurodegenerative disease, surpassed only by Alzheimer’s disease. The disease is relentless, progressive, and incurable, and there is a great need to understand its causes and develop new treatments. A distinctive pathology in most cases of Parkinson’s disease is the loss of dopaminergic neurons in the Substantia Nigra. This depletion of dopaminergic neurons has been mostly part due to the appearance of Lewy bodies containing misfolded, toxic α-synuclein within. Most recently, Parkinson’s disease has also been linked to the mitophagy pathway since genetic studies identified numerous genes linked to this disease. The processes that keep mitochondria networks healthy can be impaired in Parkinson’s disease, and mitochondria are unable to sustain proper neuronal function. Mitophagy is a selective autophagy process which targets the mitochondria for degradation. Parkinson’s disease has been shown to be linked with one of the three distinct pathways of mitophagy namely the PINK1/Parkin-dependent pathway. In this bibliographical review we will extensively discuss the work leading to delineation of this pathway as well as more recent work involving novel targeting approaches for the development of a potential new drug to halt the neurodegeneration of dopaminergic neurons and therefore treat Parkinson’s disease.