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Necrostatin-1 counteracts aluminum's neurotoxic effects
Date:8/5/2013

Amsterdam, NL, August 2, 2013 Investigators have linked aluminum accumulation in the brain as a possible contributing factor to neurodegenerative disorders such as Alzheimer's disease. A new study published in Restorative Neurology and Neuroscience sheds light on the mechanism underlying aluminum-induced neuronal cell death and identifies necrostatin-1 as a substance which counteracts several of aluminum's neurotoxic effects.

Researchers have long focused on why neurons die in degenerative diseases. One process is apoptosis, a form of gene-directed programmed cell death which removes unnecessary, aged, or damaged cells. When neurons die as a result of stroke, trauma, or other insult, the process is known as necrosis. Recently, a new type of necrosis, necroptosis (programmed necrosis), has been implicated in the cell demise process. In this report, the results of several experiments support the hypothesis that aluminum-induced neuronal cell death is, to a large extent, due to necroptosis, says lead investigator Qinli Zhang, PhD, of the Department of Occupational Health, Ministry of Education Key Laboratory, School of Public Health of Shanxi Medical University in Taiyuan China.

For instance, when aluminum was added to mouse cortical neurons grown in cell culture, the cells began to die. By adding inhibitors of apoptosis (zVAD-fmk), of autophagy (3-methyladenin, 3-MA), or of necroptosis (necrostatin-1, Nec-1), investigators showed that all treatments enhanced cell viability although Nec-1 demonstrated the strongest protection. Using fluorescent microscopy, in which surviving neural cells stain green, apoptotic cells stain orange, and necrotic cells stain red, the investigators demonstrated Al-induced cell death as well as dose-dependent reduction of necroptosis with Nec-1.

When aluminum was injected into the cerebral ventricles of living mice, brain tissue analysis revealed shrunken and abnormal-looking neurons. When Nec-1 was i
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Contact: Daphne Watrin
d.watrin@iospress.nl
31-206-883-355
IOS Press
Source:Eurekalert

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