Kinase signaling pathways as potential targets in the treatment of Parkinson's disease.
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.
Greggio
Elisa
E
Cell Biology & Gene Expression Unit, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD 20982, USA. greggio@mail.nih.gov
Singleton
Andrew
A
D000818:Animals; D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D016631:Lewy Bodies / Q000378:metabolism; D008954:Models, Biological; D009154:Mutation; D010300:Parkinson Disease / Q000378:metabolism / Q000628:therapy*; D010770:Phosphotransferases / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D011494:Protein Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry*; D040901:Proteomics / Q000379:methods*; D015398:Signal Transduction; D000099202:PTEN-Induced Putative Kinase
D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D010770:Phosphotransferases; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D011506:Proteins; D000099202:PTEN-Induced Putative Kinase; C495280:LRRK2 protein, human