PubMed:28725688 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PubMed/sourceid/28725688","sourcedb":"PubMed","sourceid":"28725688","source_url":"https://www.ncbi.nlm.nih.gov/pubmed/28725688","text":"Delaying aging is neuroprotective in Parkinson's disease: a genetic analysis in C. elegans models.\nAging is the greatest risk factor for the development of Parkinson's disease (PD). However, the role of aging in the pathogenesis of PD is not known and it is currently uncertain why the symptoms take many decades to develop when inherited mutations that cause the disease can be present from birth. We hypothesize that there are specific changes that take place during the aging process that make cells susceptible to disease-causing mutations that are well-tolerated at younger ages. If so, then interventions that increase lifespan should be beneficial in the treatment of PD. To test this hypothesis, we used the powerful genetics of C. elegans, as this worm has been used extensively in aging research. We crossed transgenic worm models of PD expressing either human mutant α-synuclein (A53T) or LRRK2 (G2019S) with the long-lived insulin-IGF1 receptor mutant, daf-2. The daf-2 mutation increased the lifespan of both PD mutants. The increase in lifespan resulting from the daf-2 mutation rescued the degeneration of dopamine neurons in both worm models of PD and importantly rescued deficits in dopamine-dependent behaviors including basal slowing, ethanol avoidance, and area-restricted searching. Increasing lifespan through daf-2 mutation also delayed the formation of small aggregates in a worm model of PD expressing α-synuclein in the body wall muscle and rescued deficits in resistance to different stresses that were present in the PD mutant worms. Overall, this work suggests that slowing down the aging process may provide an effective treatment for PD.","tracks":[{"project":"PubTator4TogoVar","denotations":[{"id":"28725688_0","span":{"begin":909,"end":915},"obj":"ProteinMutation"}],"attributes":[{"id":"28725688_0_ProteinMutation","pred":"proteinmutation","subj":"28725688_0","obj":"rs34637584"},{"subj":"28725688_0","pred":"source","obj":"PubTator4TogoVar"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"PubTator4TogoVar","color":"#a993ec","default":true}]}]}}