Paraquat and maneb induced neurotoxicity.
Parkinson's disease is a progressive neurological disorder associated with selective degeneration of nigrostriatal dopaminergic neurons. It is the most common of the neurodegenerative movement disorders, affecting approximately 1% of the population over age 65. Though the exact cause of the neurodegeneration is unknown, it has been shown that environmental factors can contribute to the onset of Parkinson's disease. Parkinsonian symptoms are seen following exposure to the herbicide paraquat, and the fungicide maneb. Furthermore, evidence clearly shows that neurodegeneration develops in environments where workers are co-exposed to paraquat and maneb. These neurotoxins cause a pesticide-induced loss of dopaminergic neurons, inducing a Parkinsonian phenotype. The specific mechanisms by which these environmental neurotoxins affect the nigral dopaminergic neurons are unknown. This gap in mechanistic understanding raises a need for further examination of their cytotoxic effects. Despite advances in pharmacotherapy that have improved quality of life, the mortality rate among Parkinson's disease sufferers remains largely unchanged. There is need for a proactive treatment strategy that could provide neuroprotection or neurorestoration. Since evidence has shown that environmental neurotoxins play an important role in nigral degeneration, there is obviously a need to take a closer look at such toxins since a greater understanding could aid in development of novel pharmacological agents with anti-parkinson and neuroprotective effects. In this review, we intend to examine the role of environmental toxins, namely paraquat and maneb, in the neurotoxicity that leads to dopamine depletion.
Thrash
Bessy
B
Department of Pharmacal Sciences, Harrison School of Pharmacy, Auburn University, Auburn, AL, USA.
Uthayathas
Subramaniam
S
Karuppagounder
Senthilkumar S
SS
Suppiramaniam
Vishnu
V
Dhanasekaran
Muralikrishnan
M
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D004347:Drug Interactions; D005659:Fungicides, Industrial / Q000633:toxicity*; D006540:Herbicides / Q000633:toxicity*; D006801:Humans; D007249:Inflammation / Q000473:pathology; D008344:Maneb / Q000633:toxicity*; D008928:Mitochondria / Q000187:drug effects; D009336:Necrosis; D020258:Neurotoxicity Syndromes / Q000473:pathology*; D018384:Oxidative Stress / Q000187:drug effects; D010269:Paraquat / Q000633:toxicity*; D010302:Parkinson Disease, Secondary / Q000473:pathology
D005659:Fungicides, Industrial; D006540:Herbicides; D008344:Maneb; D010269:Paraquat