Biochemical Mechanisms of Aluminium and Other Metals Exposure, Their Brain Entry Mechanisms, Effects on Blood Brain Barrier and Important Pharmacokinetic Parameters in Neurological Disorders

Evolution of life has resulted in a strong association between environmental metals and the biological processes taking place in the human body. Some of these metals are essential for the survival of human life, while many others can pose harmful effects on the body if exposed continuously. These toxic metals include Aluminium (Al), Arsenic (As), Lead (Pb), Mercury (Hg), Cadmium (Cd) etc. Upon entry into the brain, these metals lead to the development of many neurological disorders by increasing the levels of ROS, disturbing calcium ion efflux, causing mitochondrial dysfunction and activating an immunogenic response. These metals also cause a decrease in the levels of certain antioxidants in the brain like glutathione, superoxide dismutase and catalase. Moreover, the decrease in the level of certain genes like brain derived neurotropic factor (BDNF) due to metals neurotoxicity can also cause depletion of the memory and other cognitive functions leading to many neurodegenerative diseases like Alzheimer’s disease (AD), Parkinson’s disease (PD), etc. The following chapter explains the pharmacokinetic mechanisms involved in metals induced neurotoxicity leading to different neurological disorders.