IMR Press / FBE / Volume 5 / Issue 1 / DOI: 10.2741/E591

Frontiers in Bioscience-Elite (FBE) is published by IMR Press from Volume 13 Issue 2 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Open Access Article

Human neuromelanin: an endogenous microglial activator for dopaminergic neuron death

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1 Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100050, PR China
2 Institute of Biomedical Technologies-Italian National Research Council, Segrate (Milano), 20090, Italy
3 Neuropharmacology Section, Laboratory of Toxicology and Pharmacology, National Institute of Environmental Health Sciences/National Institutes of Health, Research Triangle Park, North Carolina, 27709, USA
4 Department of Biochemistry and Molecular Biology, College of Life Sciences, Peking University, Beijing,100871, PR China
5 Department of Physiology, Capital Medical University, Beijing, 100069, PR China

*Author to whom correspondence should be addressed.

Academic Editor: Albert Y. Sun

Front. Biosci. (Elite Ed) 2013, 5(1), 1–11; https://doi.org/10.2741/E591
Published: 1 January 2013
Abstract

Substantial evidence indicates that neuroinflammation caused by microglial activation in substantia nigra is critical in the pathogenesis of dopaminergic neurodegeneration in Parkinson’s disease (PD). Increasing data demonstrates that environmental factors such as rotenone, paraquat play pivotal roles in dopaminergic neuron death. Here, potential role and mechanism of neuromelanin (NM), a major endogenous component in dopaminergic neurons of substantia nigra, on microglial activation and associated dopaminergic neurotoxicity were investigated. Using multiple primary mesencephalic cultures, we found that HNM caused dopaminergic neurodegeneration characterized by the decreased dopamine uptake and reduced numbers and shorted dendrites. HNM was selectively toxic to dopaminergic neurons since the other types of neurons determined by either gamma-aminobutyric acid uptake and total neuronal numbers showed smaller decrease. HNM produced modest dopaminergic neurotoxicity in neuron-enriched cultures; in contrast, much greater neurotoxicity was observed in the presence of microglia. HNM morphologically activated microglia and produced proinflammatory and neurotoxic factors. Thus, HNM can be a potent endogenous activator of microglial reactivation, mediating PD progression. Hence, inhibition of microglial reactivation can be a useful strategy for PD therapy.

Keywords
Parkinson’s disease
Substantia nigra pars compacta
Human neuromelanin
Microglia
Activation
Dopaminergic neuron
Neurodegeneration
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