Potential Role of Epigenetic Mechanism in Manganese Induced Neurotoxicity.
Manganese is a vital nutrient and is maintained at an optimal level (2.5-5 mg/day) in human body. Chronic exposure to manganese is associated with neurotoxicity and correlated with the development of various neurological disorders such as Parkinson's disease. Oxidative stress mediated apoptotic cell death has been well established mechanism in manganese induced toxicity. Oxidative stress has a potential to alter the epigenetic mechanism of gene regulation. Epigenetic insight of manganese neurotoxicity in context of its correlation with the development of parkinsonism is poorly understood. Parkinson's disease is characterized by the α-synuclein aggregation in the form of Lewy bodies in neuronal cells. Recent findings illustrate that manganese can cause overexpression of α-synuclein. α-Synuclein acts epigenetically via interaction with histone proteins in regulating apoptosis. α-Synuclein also causes global DNA hypomethylation through sequestration of DNA methyltransferase in cytoplasm. An individual genetic difference may also have an influence on epigenetic susceptibility to manganese neurotoxicity and the development of Parkinson's disease. This review presents the current state of findings in relation to role of epigenetic mechanism in manganese induced neurotoxicity, with a special emphasis on the development of Parkinson's disease.
Environmental Health Division, CSIR-National Environmental Engineering Research Institute, Nagpur 440020, India.
Prashant
P
Tarale
Visvesvaraya National Institute of Technology (VNIT), Nagpur 440010, India.
Tapan
T
Chakrabarti
Environmental Health Division, CSIR-National Environmental Engineering Research Institute, Nagpur 440020, India.
Saravanadevi
S
Sivanesan
Environmental Health Division, CSIR-National Environmental Engineering Research Institute, Nagpur 440020, India.
Pravin
P
Naoghare
Environmental Health Division, CSIR-National Environmental Engineering Research Institute, Nagpur 440020, India.
Amit
A
Bafana
Environmental Health Division, CSIR-National Environmental Engineering Research Institute, Nagpur 440020, India.
Kannan
K
Krishnamurthi
D000818:Animals; D044127:Epigenesis, Genetic / Q000187:drug effects*; D005917:Globus Pallidus / Q000187:drug effects; D006801:Humans; D008345:Manganese / Q000633:toxicity*; D051379:Mice; D020258:Neurotoxicity Syndromes; D009498:Neurotoxins / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects
D009498:Neurotoxins; D008345:Manganese