Dr. Carme Espinet and colleagues at the University of Lleida, Lleida, Spain have discovered that a precursor to nerve growth factor (pro-NGF) may play a pathogenic role in Alzheimer's disease. They present these findings in the December 2009 issue of The American Journal of Pathology.
Alzheimer's disease is a degenerative, terminal form of dementia that affects over 35 million people world-wide. Oxidative stress, which occurs in the early stages of Alzheimer's disease, may modify molecules, resulting in loss or alteration of their function.
A precursor to nerve growth factor (pro-NGF) is expressed at high levels in Alzheimer's disease-affected individuals, and accumulation of pro-NGF may lead to neural cell death. Kichev et al showed that pro-NGF is modified in an Alzheimer's disease stage-dependent manner by oxidative stress and that modified pro-NGF blocked processing to mature NGF and led to neuronal cell death. Furthermore, injection of modified pro-NGF or pro-NGF derived from human Alzheimer's disease patients into mice resulted in cognitive and learning impairment, suggesting that modified pro-NGF may provide a novel pathogenic pathway for Alzheimer's disease.
Dr. Espinet's group suggests "that intra-cerebroventricular administration of AGE/ALEs modified pro-NGF to mice impairs learning tasks, thus reinforcing the idea that pro-NGF could have a relevant role in the ethiopathogenesis of the disease."
- Kichev et al. Cell Death and Learning Impairment in Mice Caused by in Vitro Modified Pro-NGF Can Be Related to Its Increased Oxidative Modifications in Alzheimer Disease. American Journal Of Pathology, 2009; DOI: 10.2353/ajpath.2009.090018
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