Elucidations of Molecular Mechanism and Mechanistic Effects of Environmental Toxicants in Neurological Disorders.

Harsh Goel, Keshav Goyal, Avanish Kumar Pandey, Mercilena Benjamin, Fahad Khan, Pratibha Pandey, Sandeep Mittan, Danish Iqbal, Mohammed Alsaweed, Wael Alturaiki, Yahya Madkhali, Mohammad Amjad Kamal, Pranay Tanwar, Tarun Kumar Upadhyay

Journal: CNS & neurological disorders drug targets 2022;22(1):84-97

PMID: 35352654

Abstract

Due to rising environmental and global public health concerns associated with environmental contamination, human populations are continually being exposed to environmental toxicants, including physical chemical mutagens widespread in our environment causing adverse consequences and inducing a variety of neurological disorders in humans. Physical mutagens comprise ionizing and non-ionizing radiation, such as UV rays, IR rays, X-rays, which produces a broad spectrum of neuronal destruction, including neuroinflammation, genetic instability, enhanced oxidative stress driving mitochondrial damage in the human neuronal antecedent cells, cognitive impairment due to alterations in neuronal function, especially in synaptic plasticity, neurogenesis repression, modifications in mature neuronal networks drives to enhanced neurodegenerative risk. Chemical Mutagens including alkylating agents (EMS, NM, MMS, and NTG), Hydroxylamine, nitrous acid, sodium azide, halouracils are the major toxic mutagen in our environment and have been associated with neurological disorders. These chemical mutagens create dimers of pyrimidine that cause DNA damage that leads to ROS generation producing mutations, chromosomal abnormalities, genotoxicity which leads to increased neurodegenerative risk. The toxicity of four heavy metal including Cd, As, Pb, Hg is mostly responsible for complicated neurological disorders in humans. Cadmium exposure can enhance the permeability of the BBB and penetrate the brain, driving brain intracellular accumulation, cellular dysfunction, and cerebral edema. Arsenic exerts its toxic effect by induction of ROS production in neuronal cells. In this review, we summarize the molecular mechanism and mechanistic effects of mutagens in the environment and their role in multiple neurological disorders.

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Address: Department of Laboratory Oncology, All India Institute of Medical Sciences, New Delhi, India.; Division of Molecular and Cellular Biology, Faculty of Biology, Ludwig Maximilians Universitat, Munchen, Germany.; Department of Biotechnology, Noida Institute of Engineering & Technology, 19, Knowledge Park-II, Institutional Area, Greater Noida, India.; Department of Cardiology, Ichan School of Medicine, Mount Sinai Hospital, One Gustave L. Levy Place, New York, USA.; Department of Medical Laboratory Sciences, College of Applied Medical Sciences, Majmaah University, Al-Majmaah, 11952, Saudi Arabia.; Institutes for Systems Genetics, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, China.; King Fahd Medical Research Center, King Abdulaziz University, Saudi Arabia.; Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Bangladesh.; Enzymoics, 7 Peterlee Place, Hebersham NSW 2770, Novel Global Community Educational Foundation, Australia.; Department of Biotechnology, Parul Institute of Applied Sciences and Cell Culture and Immunobiochemistry Lab, Centre of Research for Development, Parul University, Vadodara, Gujarat 391760, India.
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