Brain tyrosinase overexpression implicates age-dependent neuromelanin production in Parkinson's disease pathogenesis.

ABSTRACT: In Parkinson's disease (PD) there is a selective degeneration of neuromelanin-containing neurons, especially substantia nigra dopaminergic neurons. In humans, neuromelanin accumulates with age, the latter being the main risk factor for PD. The contribution of neuromelanin to PD pathogenesis remains unknown because, unlike humans, common laboratory animals lack neuromelanin. Synthesis of peripheral melanins is mediated by tyrosinase, an enzyme also present at low levels in the brain. Here we report that overexpression of human tyrosinase in rat substantia nigra results in age-dependent production of human-like neuromelanin within nigral dopaminergic neurons, up to levels reached in elderly humans. In these animals, intracellular neuromelanin accumulation above a specific threshold is associ

SUBMITTER: Carballo-Carbajal I 

PROVIDER: S-EPMC6405777 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature