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Molecular mechanism of zinc neurotoxicity in Alzheimer’s disease

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Abstract

Zinc (Zn) is an essential trace element for most organisms, including human beings. It plays a crucial role in several physiological processes such as catalytic reaction of enzymes, cellular growth, differentiation and metabolism, intracellular signaling, and modulation of nucleic acid structure. Zn containing above 50 metalloenzymes is responsible for proteins, receptors, and hormones synthesis and has a critical role in neurodevelopment. Zn also regulates excitatory and inhibitory neurotransmitters such as glutamate and GABA and is found in high concentration in the synaptic terminals of hippocampal mossy fibers that maintains cognitive function. It regulates LTP and LTD by regulation of AMPA and NMDA receptors. But an excess or deficiency of Zn becomes neurotoxic or cause impairment in growth or sexual maturation. There is mounting evidence that supports this idea of Zn becoming neurotoxic and being involved in the pathogenesis of AD. Zn dyshomeostasis in AD is an area that needs attention as moderate concentration of Zn is involved in the memory regulation via regulation of amyloid plaque. Dyshomeostasis of Zn is involved in the pathogenesis of diseases like AD, ALS, depression, PD, and schizophrenia.

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Authors and Affiliations

  1. P.G. Department of Pharmacology, College of Pharmaceutical Sciences, Govt. Medical College, Kannur, 670503, India

    Siju Ellickal Narayanan & Anju Vincent

  2. Department of Pharmaceutical Chemistry, Dr. Joseph Mar Thoma Institute of Pharmaceutical Sciences & Research, Kayamkulam, Kerala, 690503, India

    Nisha Abdul Rehuman

  3. Department of Pharmacy, Kerala University of Health Sciences, Thrissur, Kerala, India

    Seetha Harilal

  4. College of Pharmaceutical Sciences, Govt. Medical College, Kozhikode, 673008, India

    Rajalakshmi Ganesan Rajamma

  5. Department of Pharmacology, Chitkara College of Pharmacy, Chitkara University, Rajpura, Punjab, India

    Tapan Behl

  6. Department of Pharmacy, Southeast University, Dhaka, Bangladesh

    Md. Sahab Uddin

  7. Pharmakon Neuroscience Research Network, Dhaka, Bangladesh

    Md. Sahab Uddin

  8. King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia

    Ghulam Md Ashraf

  9. Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia

    Ghulam Md Ashraf

  10. Division of Drug Design and Medicinal Chemistry Research Lab, Department of Pharmaceutical Chemistry, Ahalia School of Pharmacy, Palakkad, Kerala, 678557, India

    Bijo Mathew

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  1. Siju Ellickal Narayanan
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Narayanan, S.E., Rehuman, N.A., Harilal, S. et al. Molecular mechanism of zinc neurotoxicity in Alzheimer’s disease. Environ Sci Pollut Res 27, 43542–43552 (2020). https://doi.org/10.1007/s11356-020-10477-w

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