Inflammation in Metal-Induced Neurological Disorders and Neurodegenerative Diseases

• Published in: Biological trace element research Vol. 202; no. 10; pp. 4459 - 4481
• Main Authors: Wei, Ruokun, Wei, Peiqi, Yuan, Haiyan, Yi, Xiang, Aschner, Michael, Jiang, Yue-ming, Li, Shao-jun
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.10.2024; Springer Nature B.V
• Subjects: Alzheimer's disease; Animals; Apoptosis; Astrocytes; Autophagy; Bioaccumulation; Biochemistry; Biomedical and Life Sciences; Biotechnology; Cell activation; Central nervous system; Cytokines; Defence mechanisms; Heavy metals; Humans; Inflammation - chemically induced; Inflammation - metabolism; Life Sciences; Metals; Metals - adverse effects; Metals - toxicity; Microglia; Microglia - drug effects; Microglia - metabolism; Microglia - pathology; Molecular modelling; Movement disorders; Multiple sclerosis; Nervous system; Nervous System Diseases - chemically induced; Neurodegenerative diseases; Neurodegenerative Diseases - chemically induced; Neurodegenerative Diseases - metabolism; Neuroinflammatory Diseases - chemically induced; Neuroinflammatory Diseases - metabolism; Neuroinflammatory Diseases - pathology; Neurological diseases; Neurological disorders; Neurotoxicity; Nutrition; Oncology; Oxidative stress; Oxidative Stress - drug effects; Parkinson's disease; Review; Neuroinflammation; Neurodegenerative disease; Metals; Neurological disorders
• ISSN: 0163-4984; 1559-0720; 1559-0720
• DOI: 10.1007/s12011-023-04041-z

Essential metals play critical roles in maintaining human health as they participate in various physiological activities. Nonetheless, both excessive accumulation and deficiency of these metals may result in neurotoxicity secondary to neuroinflammation and the activation of microglia and astrocytes. Activation of these cells can promote the release of pro-inflammatory cytokines. It is well known that neuroinflammation plays a critical role in metal-induced neurotoxicity as well as the development of neurological disorders, such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and multiple sclerosis (MS). Initially seen as a defense mechanism, persistent inflammatory responses are now considered harmful. Astrocytes and microglia are key regulators of neuroinflammation in the central nervous system, and their excessive activation may induce sustained neuroinflammation. Therefore, in this review, we aim to emphasize the important role and molecular mechanisms underlying metal-induced neurotoxicity. Our objective is to raise the awareness on metal-induced neuroinflammation in neurological disorders. However, it is not only just neuroinflammation that different metals could induce; they can also cause harm to the nervous system through oxidative stress, apoptosis, and autophagy, to name a few. The primary pathophysiological mechanism by which these metals induce neurological disorders remains to be determined. In addition, given the various pathways through which individuals are exposed to metals, it is necessary to also consider the effects of co-exposure to multiple metals on neurological disorders.