Neuromelanin, aging, and neuronal vulnerability in Parkinson's disease

Neuromelanin, a dark brown intracellular pigment, has long been associated with Parkinson's disease (PD). In PD, neuromelanin-containing neurons preferentially degenerate, tell-tale neuropathological inclusions form in close association with this pigment, and neuroinflammation is restricted to neuromelanin-containing areas. In humans, neuromelanin accumulates with age, which in turn is the main risk factor for PD. The potential contribution of neuromelanin to PD pathogenesis remains unknown because, in contrast to humans, common laboratory animals lack neuromelanin. The recent introduction of a rodent model exhibiting an age-dependent production of human-like neuromelanin has allowed, for the first time, for the consequences of progressive neuromelanin accumulation-up to levels reached in elderly human brains-to be assessed in vivo. In these animals, intracellular neuromelanin accumulation above a specific threshold compromises neuronal function and triggers a PD-like pathology. As neuromelanin levels reach this threshold in PD patients and presymptomatic PD patients, the modulation of neuromelanin accumulation could provide a therapeutic benefit for PD patients and delay brain aging. (c) 2019 The Author. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.