The parkin protein as a therapeutic target in Parkinson's disease

Abstract

Parkinson's disease (PD) is the most common movement disorder and the second most common neurodegenerative disease after Alzheimer's disease, affecting an increasing number of patients due to the demographic trend towards an aged population. The etiology of sporadic PD is only poorly understood, thus, the identification of genes that are reponsible for familial variants of PD was a major breakthrough. Insight into the function of these genes can promote the understanding of the molecular causes of PD and help to focus research on key biochemical pathways. Mutations in the parkin gene, encoding an E3 ubiquitin ligase, are responsible for the majority of autosomal recessive PD. Recent research revealed that parkin has a remarkably wide neuroprotective capacity, preventing cell death under various stress conditions. This property makes parkin an attractive target for therapeutic strategies to prevent or halt the loss of dopaminergic neurons.

Keywords::

• chaperone
• JNK
• Lewy body
• misfolding
• mitochondria
• NF-κB
• oxidative stress
• parkin
• Parkinson disease
• PINK1
• proteasome
• ubiquitin

Acknowledgements

Many thanks to Jörg Tatzelt and Christian Haass for stimulating discussions. I apologize to those whose work has not been cited due to space limitations.

Notes