A review on neurodegeneration in the fast-ageing killifish, the first animal model to study the natural occurrence of neuronal cell loss

Thanks to medical and technological improvements, our world population has become ever-greying. In consequence, the incidence and prevalence of age-related central nervous system neuropathies, such as Alzheimer’s (AD) and Parkinson’s disease (PD), are increasing tremendously. Despite many research efforts, the precise aetiology of these age-related neurodegenerative disorders remains elusive, highlighting the urgent need for more effective treatments. Current preclinical research mainly uses animal models that do not fully recapitulate the complex cellular context in which these diseases occur, thereby lacking good construct validity. Indeed, most investigations are performed using relatively young animals, thereby ignoring the ageing environment in which neurodegenerative diseases manifest. This points out a major hiatus in current research: a vertebrate model organism that combines the complex disease context (onset, spreading and further manifestation into functional impairment) with an ageing environment. In recent years, the African turquoise killifish has emerged as a promising novel animal model to study age-related neurodegenerative disorders that combines these essential features. In this review, we bundle all reported findings up till now and provide a detailed overview of the neurodegenerative events within the central nervous system of this teleost fish, with a focus on PD.