Unscrambling the Role of Redox-Active Biometals in Dopaminergic Neuronal Death and Promising Metal Chelation-Based Therapy for Parkinson's Disease

Biometals are all metal ions that are essential for all living organisms. About 40% of all enzymes with known structures require biometals to function correctly. The main target of damage by biometals is the central nervous system (CNS). Biometal dysregulation (metal deficiency or overload) is relat...

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Published in:International journal of molecular sciences 2023-01, Vol.24 (2), p.1256
Main Authors: Gonzalez-Alcocer, Alfredo, Duarte-Jurado, Ana Patricia, Soto-Dominguez, Adolfo, Loera-Arias, Maria de Jesus, Villarreal-Silva, Eliud Enrique, Saucedo-Cardenas, Odila, de Oca-Luna, Roberto Montes, Garcia-Garcia, Aracely, Rodriguez-Rocha, Humberto
Format: Article
Language:English
Subjects:
Apoptosis
Autophagy
Central nervous system
Chelating Agents - pharmacology
Chelating Agents - therapeutic use
Chelation
Copper
Death
Dopamine receptors
Dopaminergic Neurons - pathology
Etiology
Humans
Iron
Kinases
Lipids
Metal ions
Metals
Mitochondria
Occupational exposure
Oxidation-Reduction
Oxidative Stress
Parkinson Disease - pathology
Parkinson's disease
Proteasomes
Review
Substantia nigra
Trace Elements
Ubiquitin
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Summary:Biometals are all metal ions that are essential for all living organisms. About 40% of all enzymes with known structures require biometals to function correctly. The main target of damage by biometals is the central nervous system (CNS). Biometal dysregulation (metal deficiency or overload) is related to pathological processes. Chronic occupational and environmental exposure to biometals, including iron and copper, is related to an increased risk of developing Parkinson's disease (PD). Indeed, biometals have been shown to induce a dopaminergic neuronal loss in the substantia nigra. Although the etiology of PD is still unknown, oxidative stress dysregulation, mitochondrial dysfunction, and inhibition of both the ubiquitin-proteasome system (UPS) and autophagy are related to dopaminergic neuronal death. Herein, we addressed the involvement of redox-active biometals, iron, and copper, as oxidative stress and neuronal death inducers, as well as the current metal chelation-based therapy in PD.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms24021256