Neuromelanin and selective neuronal vulnerability to Parkinson's disease

Abstract

Neuromelanin is a unique pigment made by some human catecholamine neurons. These neurons survive with their neuromelanin content for a lifetime but can also be affected by age-related neurodegenerative conditions, as observed using new neuromelanin imaging techniques. The limited quantities of neuromelanin has made understanding its normal biology difficult, but recent rodent and primate models, as well as omics studies, have confirmed its importance for selective neuronal loss in Parkinson's disease (PD). We review the development of neuromelanin in dopamine versus noradrenaline neurons and focus on previously overlooked cellular organelles in neuromelanin formation and function. We discuss the role of neuromelanin in stimulating endogenous α-synuclein misfolding in PD which renders neuromelanin granules vulnerable, and can exacerbates other pathogenic processes.

Keywords: Lewy pathology; aging; locus coeruleus; neurodegeneration; substantia nigra; α-synuclein.