Neuromelanin and parkinson's disease

Abstract

Dark pigmented organelles, present in catecholaminergic neurons in specific brain regions, are indicated with the term neuromelanin (NM). They are complex structures, mainly comprised by granules of melanin polymer, closely associated with peptide and lipid components. Although NM is present in several animals, it is considered as a unique feature of the man due to the extremely higher degree of pigmentation, even in comparison to other primates. For a long time NM was considered an inert cellular waste product of poor interest that in the absence of mechanism of removal accumulates during the entire lifespan. Just recently, NM has received renewed attention for its role in Parkinson's disease (PD), where a selective death of the NM-containing neurons of the substantia nigra (SN) pars compacta is observed, while nonpigmented neurons are mostly spared. A physiological accumulation of NM seems to be a protective phenomenon, which prevents several neurotoxic processes. In particular, in dopaminergic neurons of SN, where no ferritin has been detected, NM appears to function as an iron storage system. However, in PD patients NM released by dying neurons can trigger a vicious circle of neuroinflammation and ensuing neuronal death. This chapter presents the structure, the production, and the development of NM, as well as the recent hypotheses about physiological NM role and its behavior in pathological conditions.