Neurotoxicity

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Neurotoxicity is a form of

drug therapies, recreational drug use, exposure to heavy metals, bites from certain species of venomous snakes, pesticides,[2][3] certain industrial cleaning solvents,[4] fuels[5] and certain naturally occurring substances. Symptoms may appear immediately after exposure or be delayed. They may include limb weakness or numbness, loss of memory, vision, and/or intellect, uncontrollable obsessive and/or compulsive behaviors, delusions, headache, cognitive and behavioral problems and sexual dysfunction. Chronic mold exposure in homes can lead to neurotoxicity which may not appear for months to years of exposure.[6] All symptoms listed above are consistent with mold mycotoxin accumulation.[7]

The term neurotoxicity implies the involvement of a neurotoxin; however, the term neurotoxic may be used more loosely to describe states that are known to cause physical brain damage, but where no specific neurotoxin has been identified.[citation needed]

The presence of

neurodegenerative diseases such as Alzheimer's disease (AD).[citation needed
]

Neurotoxic agents

Amyloid beta

AKT; this occurs as the phosphate group is bound to several sites on the protein. This phosphorylation allows AKT to interact with BAD, a protein known to cause cell death. Thus an increase in Aβ results in an increase of the AKT/BAD complex, in turn stopping the action of the anti-apoptotic protein Bcl-2, which normally functions to stop cell death, causing accelerated neuron breakdown and the progression of AD.[citation needed
]

Glutamate

mitochondria, resulting in excessive oxidative phosphorylation and production of reactive oxygen species (ROS) via the activation of nitric oxide synthase, ultimately leading to cell death. Aβ was also found aiding this route to neurotoxicity by enhancing neuron vulnerability to glutamate.[citation needed
]

Oxygen radicals

The formation of

postmitotic
cells, meaning that they live with accumulated damage over the years, accumulation of ROS is fatal. Thus, increased levels of ROS age neurons, which leads to accelerated neurodegenerative processes and ultimately the advancement of AD.

Dopaminergic Neurotoxicity

Endogenous

The endogenously produced autotoxin metabolite of dopamine, 3,4-Dihydroxyphenylacetaldehyde (DOPAL), is a potent inducer of programmed cell death (apoptosis) in dopaminergic neurons.[8] DOPAL may play an important role in the pathology of Parkinson's disease.[9][10]

Drug induced

Certain drugs, most famously the pesticide and metabolite MPP+ (1-methyl-4-phenylpyridin-1-ium) can induce Parkinson's disease by destroying dopaminergic neurons in the substantia nigra.[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.[13] The neurotoxicity of MPP+ was first investigated after MPTP was produced as a contaminant in the pethidine synthesized by a chemistry graduate student, who injected the contaminated drug and developed overt Parkinson's within weeks.[12][11] Discovery of the mechanism of toxicity was an important advance in the study of Parkinson's disease, and the compound is now used to induce the disease in research animals.[11][14]

Prognosis

The prognosis depends upon the length and degree of exposure and the severity of neurological injury. In some instances, exposure to neurotoxins or neurotoxicants can be fatal. In others, patients may survive but not fully recover. In other situations, many individuals recover completely after treatment.[15]

The word neurotoxicity (

combining forms of neuro- + tox- + -icity, yielding "nervous tissue
poisoning".

See also

References

Further reading