Kinase signaling pathways as potential targets in the treatment of Parkinson’s disease

Abstract

Parkinson’s disease (PD) is a severe, progressive, age-associated, neurodegenerative disorder. Current therapies are symptomatic and not effective at halting or significantly slowing the disease progress. The search for etiologic-based therapies has focused largely on genetic findings made in familial forms of this disease. Mutations of five genes have been unequivocally linked to PD; two of these, LRRK2 and PINK1, encode kinases and as such are attractive tools with which to understand the disease process; furthermore, preliminary functional data suggests that these proteins, or the pathways in which they are involved, are viable therapeutic targets. Here we explore the current data and thoughts regarding LRRK2 and PINK1 and discuss further avenues of research to understand the pathologic effects of mutations at these loci and potential points of therapeutic intervention, such as within these kinases or in associated pathways such as Jun N-terminal kinase and Akt pathways.

Keywords::

• genetics
• inhibitor
• kinase
• LRRK2
• Parkinson’s disease
• PINK1

Acknowledgement

We would like to thank Mark Cookson and Patrick Lewis for helpful discussions in the writing of this manuscript.

Financial & competing interests disclosure

This work was supported by the Intramural program of the National Institute on Aging, National Institutes of Health, Department of Health and Human Services. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.