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Publication : The effects of short-term JNK inhibition on the survival and growth of aged sympathetic neurons.

First Author  Guha I Year  2016
Journal  Neurobiol Aging Volume  46
Pages  138-48 PubMed ID  27490965
Mgi Jnum  J:239463 Mgi Id  MGI:5828953
Doi  10.1016/j.neurobiolaging.2016.06.016 Citation  Guha I, et al. (2016) The effects of short-term JNK inhibition on the survival and growth of aged sympathetic neurons. Neurobiol Aging 46:138-48
abstractText  During the course of normal aging, certain populations of nerve growth factor (NGF)-responsive neurons become selectively vulnerable to cell death. Studies using dissociated neurons isolated from neonates have shown that c-Jun N-terminal kinases (JNKs) are important in regulating the survival and neurite outgrowth of NGF-responsive sympathetic neurons. Unlike neonatal neurons, adult sympathetic neurons are not dependent on NGF for their survival. Moreover, the NGF precursor, proNGF, is neurotoxic for aging but not young adult NGF-responsive neurons. Because of these age-related differences, the effects of JNK inhibition on the survival and growth of sympathetic neurons isolated from aged mice were studied. Aged neurons, as well as glia, were found to be dependent on JNK for their growth but not their survival. Conversely, proNGF neurotoxicity was JNK-dependent and mediated by the p75-interacting protein NRAGE, whereas neurite outgrowth was independent of NRAGE. These results have implications for the potential use of JNK inhibitors as therapies for ameliorating age-related neurodegenerative disease.
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