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

Abstract

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.

Multifunctional Metallothioneins as a Target for Neuroprotection in Parkinson’s Disease

“…Since Fe accumulation in the brain has been linked to PD, metal chelation could be a promising therapeutic approach [ 53 ]. Indeed, experimental studies using parkinsonian models have shown that Fe chelation reduces pathological α-synuclein accumulation [ 54 ] and oxidative stress [ 55 , 56 ].…”

One‐Pot Synthesis of Nanoflower‐Like Zn2SnS4 as Nanozymes for Highly Sensitive Electrochemical Detection of H2O2 Released by Living Cells

“…[1] The concentration level of H 2 O 2 serves as a vital biological parameter for monitoring the physiological balance of living cells, and the deviations of the concentration levels can result in cellular dysfunction, cellular variability and apoptosis, potentially leading to serious health conditions including myocardial infarction, Parkinson's disease, and various cancers. [2,3] The development of efficient and reliable modus for the sensitive and selective detection of H 2 O 2 under physiological conditions is of paramount importance. In the past two decades, a variety of methods have been utilized to H 2 O 2 detection, including colorimetry, [4] spectrometry, [5] chemiluminescence, [6] positron emission tomography, [7] electrochemical methods, [8] and more comparison of the analytical performance of other assay methods on H 2 O 2 detection have been exhibited in Table S-1.…”

“…Hydrogen peroxide (H 2 O 2 ) is a crucial small molecule mediator widely involved in cell growth and signal transduction [1] . The concentration level of H 2 O 2 serves as a vital biological parameter for monitoring the physiological balance of living cells, and the deviations of the concentration levels can result in cellular dysfunction, cellular variability and apoptosis, potentially leading to serious health conditions including myocardial infarction, Parkinson's disease, and various cancers [2,3] . The development of efficient and reliable modus for the sensitive and selective detection of H 2 O 2 under physiological conditions is of paramount importance.…”