Cited by 659Parkinson's Disease Mechanisms and TreatmentsNeurological diseases and metabolismIron Metabolism and Disorders

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Interactions of iron, dopamine and neuromelanin pathways in brain aging and Parkinson's disease

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Zucca, Fabio A., Segura-Aguilar, Juan, Ferrari, Emanuele, Muñoz, Patricia, Paris, Irmgard, Sulzer, David, Sarna, Tadeusz, Casella, Luigi, Zecca, Luigi·2017·Progress in Neurobiology

DOI 10.1016/j.pneurobio.2015.09.012PMC PMC4826627

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Abstract

There are several interrelated mechanisms involving iron, dopamine, and neuromelanin in neurons. Neuromelanin accumulates during aging and is the catecholamine-derived pigment of the dopamine neurons of the substantia nigra and norepinephrine neurons of the locus coeruleus, the two neuronal populations most targeted in Parkinson's disease. Many cellular redox reactions rely on iron, however an altered distribution of reactive iron is cytotoxic. In fact, increased levels of iron in the brain of Parkinson's disease patients are present. Dopamine accumulation can induce neuronal death; however, excess dopamine can be removed by converting it into a stable compound like neuromelanin, and this process rescues the cell. Interestingly, the main iron compound in dopamine and norepinephrine neurons is the neuromelanin-iron complex, since neuromelanin is an effective metal chelator. Neuromelanin serves to trap iron and provide neuronal protection from oxidative stress. This equilibrium between iron, dopamine, and neuromelanin is crucial for cell homeostasis and in some cellular circumstances can be disrupted. Indeed, when neuromelanin-containing organelles accumulate high load of toxins and iron during aging a neurodegenerative process can be triggered. In addition, neuromelanin released by degenerating neurons activates microglia and the latter cause neurons death with further release of neuromelanin, then starting a self-propelling mechanism of neuroinflammation and neurodegeneration. Considering the above issues, age-related accumulation of neuromelanin in dopamine neurons shows an interesting link between aging and neurodegeneration.

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Authors: Zucca, F. A., Segura-Aguilar, J., Ferrari, E., Muñoz, P., Paris, I., Sulzer, D., Sarna, T., Casella, L., & Zecca, L.
Affiliations: Institute of Biomedical Technologies (IT)
University of Chile (CL)
Universidad Santo Tomás (CL)
Columbia University Irving Medical Center (US)
Jagiellonian University (PL)
University of Pavia (IT)
Corresponding author: Zecca, Luigi
ORCID: Zucca, Fabio A.
Segura-Aguilar, Juan
Ferrari, Emanuele
Muñoz, Patricia
Paris, Irmgard
Sulzer, David
Sarna, Tadeusz
Casella, Luigi
Zecca, Luigi
Venue: Progress in Neurobiology
Publisher: Elsevier BV
Published: 2017-08
Volume: 155
Pages: 96-119
ISSN: 0301-0082 (ISSN-L)
DOI: 10.1016/j.pneurobio.2015.09.012
PMC: PMC4826627
OpenAlex: W1913653254
Cited by: 659
References: 350
Citations by year: 2026: 43 · 2025: 59 · 2024: 58 · 2023: 73 · 2022: 74 · 2021: 72 · 2020: 70 · 2019: 77 · 2018: 53 · 2017: 46
FWCI: 5.75
Type: journal article
Language: en
Open access: green
europepmc.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Progress in Neurobiology (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Jagiellonian University Repository (Jagiellonian University) (submittedVersion, cc-by-nc-nd)
Universidad de Chile (submittedVersion, cc-by-nc-nd)
Funders: National Institute on Drug Abuse (P01DA010154, R01DA007418)
Topics: Health Sciences › Medicine › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
Life Sciences › Neuroscience › Neurology › Neurological diseases and metabolism
Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
Keywords: neuromelanin, iron, dopamine, brain aging, Parkinson's disease, substantia nigra, locus coeruleus, noradrenergic neurons, oxidative stress, metal chelation, neuroinflammation, microglial activation, neurodegeneration, redox homeostasis
MeSH terms: Aging, Animals, Dopamine, Humans, Iron, Melanins, Parkinson Disease

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Interactions of iron, dopamine and neuromelanin pathways in brain aging and Parkinson's disease

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