Journal
HUMAN MOLECULAR GENETICS
Volume 23, Issue 22, Pages 5916-5927Publisher
OXFORD UNIV PRESS
DOI: 10.1093/hmg/ddu316
Keywords
-
Funding
- BBSRC
- Research into Ageing
- Wellcome Trust
- National Institutes of Health National Center for Research Resources (NCRR)
- National Bio-Resource Project of C. elegans
- University of Liverpool Library
- BBSRC [BB/J005843/1] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [BB/J005843/1] Funding Source: researchfish
Ask authors/readers for more resources
Adult onset neuronal lipofuscinosis (ANCL) is a human neurodegenerative disorder characterized by progressive neuronal dysfunction and premature death. Recently, the mutations that cause ANCL were mapped to the DNAJC5 gene, which encodes cysteine string protein alpha. We show here that mutating dnj-14, the Caenorhabditis elegans orthologue of DNAJC5, results in shortened lifespan and a small impairment of locomotion and neurotransmission. Mutant dnj-14 worms also exhibited age-dependent neurodegeneration of sensory neurons, which was preceded by severe progressive chemosensory defects. A focussed chemical screen revealed that resveratrol could ameliorate dnj-14 mutant phenotypes, an effect mimicked by the cAMP phosphodiesterase inhibitor, rolipram. In contrast to other worm neurodegeneration models, activation of the Sirtuin, SIR-2.1, was not required, as sir-2.1; dnj-14 double mutants showed full lifespan rescue by resveratrol. The Sirtuin-independent neuroprotective action of resveratrol revealed here suggests potential therapeutic applications for ANCL and possibly other human neurodegenerative diseases.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available