Neurotoxicity is a form of toxicity in which a biological, chemical, or physical agent produces an adverse effect on the structure or function of the central and/or peripheral nervous system.
Some of the most common naturally occurring brain toxins that lead to neurotoxicity as a result of long term drug use are amyloid beta (Aβ), glutamate, dopamine, and oxygen radicals.
Some of the symptoms that result from cell death include loss of motor control, cognitive deterioration and autonomic nervous system dysfunction.
[citation needed] Amyloid beta (Aβ) was found to cause neurotoxicity and cell death in the brain when present in high concentrations.
Aβ was found manipulating the level of nicotine in the brain along with the MAP kinase, another signaling receptor, to cause cell death.
Another way Aβ causes cell death is through the phosphorylation of AKT; this occurs as the phosphate group is bound to several sites on the protein.
Naturally, the body utilizes a defensive mechanism to diminish the fatal effects of the reactive species by employing certain enzymes to break down the ROS into small, benign molecules of simple oxygen and water.
However, this breakdown of the ROS is not completely efficient; some reactive residues are left in the brain to accumulate, contributing to neurotoxicity and cell death.
The endogenously produced autotoxin metabolite of dopamine, 3,4-Dihydroxyphenylacetaldehyde (DOPAL), is a potent inducer of programmed cell death (apoptosis) in dopaminergic neurons.
[11] MPP+ interacts with the electron transport chain in the mitochondria to generate reactive oxygen species which cause generalized oxidative damage and ultimately cell death.
[12][13] MPP+ is produced by monoamine oxidase B as a metabolite of MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine), and its toxicity is particularly significant to dopaminergic neurons because of an active transporter on those cells that bring it into the cytoplasm.