Document Detail


Manganese neurotoxicity: a mechanistic hypothesis.
MedLine Citation:
PMID:  10385907     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
This review provides a summary of the presentations and abstracts presented at the 15th International Neurotoxicology Conference which may contribute to an understanding of the mechanism and pathogenesis of manganese (Mn2+) neurotoxicity. We propose that an understanding of the pathogenesis of Mn2+ neurotoxicity must incorporate data on (1) the factors controlling Mn2+ uptake and distribution within the CNS, (2) account for the apparent selectivity of dopaminergic neurons, (3) analyze the role of mitochondrial dysfunction and (4) provide data to support or refute the role of oxidative injury in the genesis of toxicity. We propose a multifactor hypothesis coupling Mn2+ uptake with coincident transport of aluminum and iron. Selectivity of dopaminergic neurons is dependent upon interactions of Mn2+ with dopamine transport and the role of Mn2+ as a pro-oxidative toxicant in conjunction with changes in iron concentration. Within the synaptic milieu, Mn(2+)-mitochondrial interaction will influence mitochondrial--Ca2+ transport kinetics leading to defective mitochondrial function, decreased oxidative phosphorylation, decreased ATP and accumulation of reactive oxygen species. Under the influence of excessive depolarization, energy failure will occur leading to secondary activation of an excitotoxic state. These conceptual ideas provide for mechanistic based hypotheses and testing and are likely to lead to rational therapeutic avenues directed against Mn2+ neurotoxicity.
Authors:
M A Verity
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Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  Neurotoxicology     Volume:  20     ISSN:  0161-813X     ISO Abbreviation:  Neurotoxicology     Publication Date:    1999 Apr-Jun
Date Detail:
Created Date:  1999-09-03     Completed Date:  1999-09-03     Revised Date:  2005-11-16    
Medline Journal Info:
Nlm Unique ID:  7905589     Medline TA:  Neurotoxicology     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  489-97     Citation Subset:  IM    
Affiliation:
Department of Pathology and Laboratory Medicine, UCLA Medical Center 90095-1732, USA. averity@pathology.medsch.ucla.edu
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MeSH Terms
Descriptor/Qualifier:
Animals
Calcium / pharmacokinetics
Dopamine Antagonists / pharmacology
Globus Pallidus / drug effects,  metabolism*
Humans
Iron / pharmacokinetics
Manganese / pharmacokinetics
Manganese Poisoning*
Mitochondria / drug effects*
Nervous System Diseases / chemically induced*
Oxidative Stress / drug effects,  physiology*
Synapses / drug effects*
Chemical
Reg. No./Substance:
0/Dopamine Antagonists; 7439-89-6/Iron; 7439-96-5/Manganese; 7440-70-2/Calcium

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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