Neuromelanin and selective neuronal vulnerability to Parkinson’s disease

Abstract

Aging; Neurodegeneration; Substantia nigra

Envelliment; Neurodegeneració; Substància negra

Envejecimiento; Neurodegeneración; Sustancia negra

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.

This work was supported in part by Aligning Science Across Parkinson’s [020505] through the Michael J. Fox Foundation for Parkinson’s Research (MJFF) and also by funding to GH from the National Health and Medical Research Council of Australia [Investigator Grant 1176607]. For open access, the authors have applied a CC BY public copyright license to all Author Accepted Manuscripts arising from this submission. We would like to thank Heidi Cartwright for assistance with the figures.