The Neuromelanin Paradox and Its Dual Role in Oxidative Stress and Neurodegeneration

Antioxidants

Alejandra Kun¹  Olga Calero²  Alexandra Moreno-García²  Miguel Calero² 

[1] Biochemistry Section, Science School, Universidad de la República, 11400 Montevideo, Uruguay;Chronic Disease Programme, Instituto de Salud Carlos III, 28029 Madrid, Spain;

关键词: reactive oxygen species (ROS);    neuromelanin (NM);    oxidative stress;    neurodegeneration;    immune response;   

DOI  :  10.3390/antiox10010124

来源: DOAJ

【 摘 要 】

Aging is associated with an increasing dysfunction of key brain homeostasis mechanisms and represents the main risk factor across most neurodegenerative disorders. However, the degree of dysregulation and the affectation of specific pathways set apart normal aging from neurodegenerative disorders. In particular, the neuronal metabolism of catecholaminergic neurotransmitters appears to be a specifically sensitive pathway that is affected in different neurodegenerations. In humans, catecholaminergic neurons are characterized by an age-related accumulation of neuromelanin (NM), rendering the soma of the neurons black. This intracellular NM appears to serve as a very efficient quencher for toxic molecules. However, when a neuron degenerates, NM is released together with its load (many undegraded cellular components, transition metals, lipids, xenobiotics) contributing to initiate and worsen an eventual immune response, exacerbating the oxidative stress, ultimately leading to the neurodegenerative process. This review focuses on the analysis of the role of NM in normal aging and neurodegeneration related to its capabilities as an antioxidant and scavenging of harmful molecules, versus its involvement in oxidative stress and aberrant immune response, depending on NM saturation state and its extracellular release.

【 授权许可】

Unknown