2015
DOI: 10.1038/npjparkd.2015.22
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Delaying aging is neuroprotective in Parkinson’s disease: a genetic analysis in C. elegans models

Abstract: Aging 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 tha… Show more

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Cited by 77 publications
(110 citation statements)
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“…Even dominantly inherited genetic forms of PD require the passage of time, often decades, for PD symptoms to emerge. Without aging, degenerative changes in DA neurons are not fully expressed in PD genetic models in C. elegans and human iPSCs, and the expression of genes strongly associated with PD are uniformly regulated by aging in a disease‐promoting direction . On the flip side, aging is not PD.…”
Section: Discussionmentioning
confidence: 99%
See 1 more Smart Citation
“…Even dominantly inherited genetic forms of PD require the passage of time, often decades, for PD symptoms to emerge. Without aging, degenerative changes in DA neurons are not fully expressed in PD genetic models in C. elegans and human iPSCs, and the expression of genes strongly associated with PD are uniformly regulated by aging in a disease‐promoting direction . On the flip side, aging is not PD.…”
Section: Discussionmentioning
confidence: 99%
“…The worm C. elegans provides a powerful experimental approach for studying the genetics of aging and PD. A recent report by Cooper and colleagues examined the effects of delaying aging on the phenotype of worms harboring human PD mutations in α‐syn or leucine‐rich repeat kinase 2 (LRRK2), specifically in DA neurons. PD‐mutant worms exhibited normal development and lifespan, but expressed a phenotype that included deficits in dopamine‐dependent behaviors, greater sensitivity to stressors, and accelerated DA neuron degeneration.…”
Section: Additional Considerationsmentioning
confidence: 99%
“…C. elegans overexpressing human WT or mutant α-syn using pan-neuronal-(aex-3) or dopamine-directed (dat) promoter present significant decrease in the number of dopaminergic neurons (Table 5) in the cephalic neurons, anterior deirid and posterior deirid (Cao, Yuan, Pehek, Moise & Huang, 2010;Cooper, Dues, Spielbauer, Machiela & Senchuk, 2015;Lakso et al, 2003). Interestingly, overexpression of human WT or mutant LRKK2 protein (G2019S, R1441C) in C. elegans is associated with a drop in the levels of DA and DA transporters, which is more pronounced in transgenic organisms bearing the mutated forms of the gene (Table 7) (Saha, Guillily, Ferree, Lanceta & Chan, 2009;Yao et al, 2010).…”
Section: Non-motor Deficitsmentioning
confidence: 99%
“…References in which this protocol was used: Van Raamsdonk and Hekimi, 2009; 2012; Van Raamsdonk et al, 2010; Cooper et al, 2015; Schaar et al, 2015; Dues et al, 2016; Machiela et al, 2016.…”
Section: Methodsmentioning
confidence: 99%