Neurotoxicity
This article includes a list of general references, but it lacks sufficient corresponding inline citations. (August 2014) |
Neurotoxicity is a form of
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
Neurotoxic agents
Amyloid beta
Glutamate
Oxygen radicals
The formation of
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 ( poisoning".
See also
References
Further reading
- Akaike, Akinori; Takada-Takatori, Yuki; Kume, Toshiaki; Izumi, Yasuhiko (January 2010). "Mechanisms of Neuroprotective Effects of Nicotine and Acetylcholinesterase Inhibitors: Role of α4 and α7 Receptors in Neuroprotection". Journal of Molecular Neuroscience. 40 (1–2): 211–216. S2CID 7279060.
- Buckingham, Steven D.; Jones, Andrew K.; Brown, Laurence A.; Sattelle, David B. (March 2009). "Nicotinic Acetylcholine Receptor Signalling: Roles in Alzheimer's Disease and Amyloid Neuroprotection". Pharmacological Reviews. 61 (1): 39–61. PMID 19293145.
- Huber, Anke; Stuchbury, Grant; Burkle, Alexander; Burnell, Jim; Munch, Gerald (1 February 2006). "Neuroprotective Therapies for Alzheimers Disease". Current Pharmaceutical Design. 12 (6): 705–717. PMID 16472161.
- Takada-Takatori, Yuki; Kume, Toshiaki; Izumi, Yasuhiko; Ohgi, Yuta; Niidome, Tetsuhiro; Fujii, Takeshi; Sugimoto, Hachiro; Akaike, Akinori (2009). "Roles of Nicotinic Receptors in Acetylcholinesterase Inhibitor-Induced Neuroprotection and Nicotinic Receptor Up-Regulation". Biological & Pharmaceutical Bulletin. 32 (3): 318–324. PMID 19252271.
- Takada-Takatori, Yuki; Kume, Toshiaki; Sugimoto, Mitsuhiro; Katsuki, Hiroshi; Sugimoto, Hachiro; Akaike, Akinori (September 2006). "Acetylcholinesterase inhibitors used in treatment of Alzheimer's disease prevent glutamate neurotoxicity via nicotinic acetylcholine receptors and phosphatidylinositol 3-kinase cascade". Neuropharmacology. 51 (3): 474–486. S2CID 31409248.
- Shimohama, Shun (2009). "Nicotinic Receptor-Mediated Neuroprotection in Neurodegenerative Disease Models". Biological & Pharmaceutical Bulletin. 32 (3): 332–336. PMID 19252273.
- Ryan, Melody; Kennedy, Kara A. (2009). "Neurotoxic Effects of Pharmaceutical Agents II: Psychiatric Agents". Clinical Neurotoxicology. pp. 348–357. ISBN 978-0-323-05260-3.
- Lerner, David P.; Tadevosyan, Aleksey; Burns, Joseph D. (1 November 2020). "Toxin-Induced Subacute Encephalopathy". Neurologic Clinics. 38 (4): 799–824. S2CID 222301922.