2. Academic Validation
  3. The effects of short-term JNK inhibition on the survival and growth of aged sympathetic neurons

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

  • Neurobiol Aging. 2016 Oct:46:138-48. doi: 10.1016/j.neurobiolaging.2016.06.016.
Isa Guha 1,  Ivana Slamova 1,  Soyon Chun 1,  Arthur Clegg 1,  Michal Golos 1,  Chris Thrasivoulou 2,  J Paul Simons 3,  Raya Al-Shawi 4
Affiliations

Affiliations

  • 1 Genetics Unit and Wolfson Drug Discovery Unit, Centre for Amyloidosis and Acute Phase Proteins, Division of Medicine, University College London, Royal Free Campus, London, UK.
  • 2 Research Department of Cell and Developmental Biology, University College London, London, UK.
  • 3 Genetics Unit and Wolfson Drug Discovery Unit, Centre for Amyloidosis and Acute Phase Proteins, Division of Medicine, University College London, Royal Free Campus, London, UK. Electronic address: [email protected].
  • 4 Genetics Unit and Wolfson Drug Discovery Unit, Centre for Amyloidosis and Acute Phase Proteins, Division of Medicine, University College London, Royal Free Campus, London, UK. Electronic address: [email protected].
PMID: 27490965 DOI: 10.1016/j.neurobiolaging.2016.06.016
Abstract

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.

Keywords

Aging; JNK; NGF; NRAGE; Neurons; ProNGF.

Figures
Products