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

Publication date: Available online 5 July 2016
Source:Neurobiology of Aging
Author(s): Isa Guha, Ivana Slamova, Soyon Chun, Arthur Clegg, Michal Golos, Chris Thrasivoulou, J. Paul Simons, Raya Al-Shawi
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 was 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, while 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.



from #ORL via xlomafota13 on Inoreader http://ift.tt/29phuPE
via IFTTT