Funding agencies: This work was supported, in part, by the Intramural Research Program of the National Institute on Aging, National Institutes of Health, Department of Health and Human Services (project no.: Z01 AG000949-06). This study was supported by grants from the “Internationaal Parkinson Fonds,” The Netherlands, and the Netherlands Organization for Scientific Research (NWO, VIDI grant; to V.B.).
The genetics of Parkinson's disease: Progress and therapeutic implications
Article first published online: 6 FEB 2013
Copyright © 2013 Movement Disorders Society
Special Issue: The Vatican Conference on Neuroprotection in Parkinson's Disease
Volume 28, Issue 1, pages 14–23, January 2013
How to Cite
Singleton, A. B., Farrer, M. J. and Bonifati, V. (2013), The genetics of Parkinson's disease: Progress and therapeutic implications. Mov. Disord., 28: 14–23. doi: 10.1002/mds.25249
Relevant conflicts of interest/financial disclosures: Nothing to report.
Full financial disclosures and author roles may be found in the online version of this article.
- Issue published online: 6 FEB 2013
- Article first published online: 6 FEB 2013
- Manuscript Accepted: 20 SEP 2012
- Manuscript Revised: 22 AUG 2012
- Manuscript Received: 25 APR 2012
- Parkinson-s disease;
The past 15 years has witnessed tremendous progress in our understanding of the genetic basis for Parkinson's disease (PD). Notably, whereas most mutations, such as those in SNCA, PINK1, PARK2, PARK7, PLA2G6, FBXO7, and ATP13A2, are a rare cause of disease, one particular mutation in LRRK2 has been found to be common in certain populations. There has been considerable progress in finding risk loci. To date, approximately 16 such loci exist; notably, some of these overlap with the genes known to contain disease-causing mutations. The identification of risk alleles has relied mostly on the application of revolutionary technologies; likewise, second-generation sequencing methods have facilitated the identification of new mutations in PD. These methods will continue to provide novel insights into PD. The utility of genetics in therapeutics relies primarily on leveraging findings to understand the pathogenesis of PD. Much of the investigation into the biology underlying PD has used these findings to define a pathway, or pathways, to pathogenesis by trying to fit disparate genetic defects onto the same network. This work has had some success, particularly in the context of monogenic disease, and is beginning to provide clues about potential therapeutic targets. Approaches toward therapies are also being provided more directly by genetics, notably by the reduction and clearance of alpha-synuclein and inhibition of Lrrk2 kinase activity. We believe this has been an exciting, productive time for PD genetics and, furthermore, that genetics will continue to drive the etiologic understanding and etiology-based therapeutic approaches in this disease. © 2013 Movement Disorder Society