Does Nothobranchius furzeri Gonarezhou die from a Parkinson’s-like Disease?

Neurodegeneration has diverse molecular causes. α-synucleinopathies are implicated in at least three neurodegenerative diseases: Parkinson’s Disease, Dementia with Lewy bodies and Multiple System Atrophy. Age-related increases in α-synuclein and its oligomers have been observed in short-lived Nothobranchius furzeri. N. furzeri Gonarezhou, with a lifespan of 9–12 weeks, is a new model organism for aging research. With age the fish develops motor deficiencies that can be explained by the degeneration of its dopaminergic system. The author proposes to test the hypothesis that N. furzeri Gonarezhou are dying from an α-synucleinopathy, in particular: a Parkinson’s-like Disease. Additionally, the effects of lifespan-altering interventions (calorie restriction, resveratrol and NT-020) on N. furzeri age-related neuropathology will be examined. NT-020 has been shown to reduce the αsynucleinopathy burden of aged N. furzeri as well as extend lifespan. Histological samples will be analyzed for the identification and localization of dopaminergic neurons as well as neuropathologies (α-synucleinopathies, neurofibrillary tangles, gliosis and β-amyloid plaques). The location and staging of the pathologies will be elucidated, as well as how the pattern of the pathology differs with age between the Gonarezhou and wild-derived strains. In addition, the effect of anti-aging treatments (e.g. NT-020) on pathology burden and pattern will be investigated. NT-020 is already recognized as a safe and cost-effective supplement that slows the progression of age-associated cognitive decline. This research will determine whether NT-020 may also find application in the treatment and prevention of human α-synucleinopathies.