The aging brain: impact of heavy metal neurotoxicity

Abstract

The aging process is accompanied by critical changes in cellular and molecular functions, which upset the homeostatic balance in the central nervous system. Accumulation of metals renders the brain susceptible to neurotoxic insults by mechanisms such as mitochondrial dysfunction, neuronal calcium-ion dyshomeostasis, buildup of damaged molecules, compromised DNA repair, reduction in neurogenesis, and impaired energy metabolism. These hallmarks have been identified to be responsible for neuronal injuries, resulting in several neurological disorders. Various studies have shown solid associations between metal accumulation, abnormal protein expressions, and pathogenesis of neurodegenerative diseases such as Parkinson’s disease, Alzheimer’s disease, Huntington’s disease, and Amyotrophic lateral sclerosis. This review highlights metals (such as manganese, zinc, iron, copper, and nickel) for their accumulation, and consequences in the development of neurological disorders, in relation to the aging brain.

Keywords:

• Neurotoxicity
• aging
• metal accumulation
• brain diseases
• mitochondrial dysfunction
• DNA damage oxidative stress

Acknowledgements

The authors gratefully acknowledge the valuable and extensive critiques of the three anonymous reviewers that were selected by the Editor. Also, we acknowledge the vital feedback received from the Editor. These critiques were very helpful in revising and improving the manuscript.

Declaration of interest

Authors involved in the preparation of this manuscript did not receive any compensation from any source and declare that they have no potential conflict of interest. The preparation of this review was conducted during normal course of authors’ employment. All authors were involved in preparing the manuscript with contributorship as follows: Conception and design – OMI; Manuscript draft – CWI, OMA, OKI; Critical revision of manuscript – OMI, MA. All authors approved final manuscript draft. The authors have the sole responsibility for the writing and content of the manuscript. None of the authors have been involved in any legal, advocacy or regulatory roles in the last 5 years that is related to the contents of this review. The authors declare that there is no conflict of interest regarding the publication of this article.

Additional information

Funding

This work was supported by the International Brain Research Organization (IBRO) and National Institute of Health (NIH), respectively [to OMI and MA]. OMI acknowledges the Young IBRO Regions Connecting Awards toward collaborative activities between The Neuro- Lab, Federal University of Technology Akure, Nigeria, and Aschner’s Lab, Albert Einstein College of Medicine, USA. MA is supported by National Institute of Health (NIH), USA [grant number NIEHS R01 10563], grant number NIEHS R01 07331], [grant number NIEHS R01 020852].