Chronic degenerative models of Parkinson’s disease.

The neurodegenerative diseases are difficult to model in animals because either the behavioural and cognitive deficits are peculiar to human beings (e.g. Alzheimer’s dementia) or no naturally occurring animal equivalent exists (such as Parkinson’s disease, PD). Typically also, these human diseases develop slowly, over many times the lifespan of the typical laboratory rodent. Current animal models of PD either replicate a rare genetic modification which causes over-expression of mutant human alpha-synuclein (α-syn) or employ an acute toxic insult to cause severe damage to the substantia nigra pars compacta (SN) in order to reproduce some behavioural or histopathological features of the disease. By and large these models fail to mimic the progressive nature of the human disease and reveal little about the mechanism of chronic neurodegeneration. We have focused on a TRIAD of candidate molecules: iron, dopamine (DA) and α-syn, which co-localize in the SN and which in-vitro modelling suggests may act co-operatively to propagate a neurotoxic oxidative cascade.