Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

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

Version 1 : Received: 30 November 2020 / Approved: 1 December 2020 / Online: 1 December 2020 (15:02:04 CET)

A peer-reviewed article of this Preprint also exists.

Moreno-García, A.; Kun, A.; Calero, M.; Calero, O. The Neuromelanin Paradox and Its Dual Role in Oxidative Stress and Neurodegeneration. Antioxidants 2021, 10, 124. Moreno-García, A.; Kun, A.; Calero, M.; Calero, O. The Neuromelanin Paradox and Its Dual Role in Oxidative Stress and Neurodegeneration. Antioxidants 2021, 10, 124.

Journal reference: Antioxidants 2021, 10, 124
DOI: 10.3390/antiox10010124

Abstract

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, antibiotics) 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 catecholaminergic metabolism due to its capability as a pro-oxidant and other harmful molecules, versus its involvement in oxidative stress and aberrant immune response, which it is highly dependent on NM saturation state and its extracellular release.

Subject Areas

reactive oxygen species (ROS), neuromelanin (NM), oxidative stress, neurodegeneration, immune response

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