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Journal of Glycobiology | ISSN: 2168-958X | Volume 7
Glycobiology & Glycoproteomics
5
th
International Conference on
&
August 27-28, 2018 | Toronto, Canada
Molecular Biology & Nucleic Acids
3
rd
International Conference on
Hydralazine induces stress resistance and extends Caenorhabditis elegans lifespan by activating the NRF2/
SKN-1 signaling pathway
A
dvances in modern medicine have led to increased life expectancy. As an aging population increases, finding a cure for an
age-related cognitive decline is becoming more and more important. A hallmark of neurodegenerative diseases, one of the
main pathologies underlying age-related dementia, is the deposition of insoluble proteins in cells of the neuromuscular system
causing proteotoxicity. Substantial literature suggests that the primary inducer of proteotoxicity in aging is chronic deterioration
of defense machinery including antioxidant, heat shock, and degradation systems. Deterioration of defense machinery create
imbalances in aggregation and clearance pathways leading to proteotoxicity by altering aggregate dynamics, localization and
aberrant interactions. One of themain targets of toxic proteins aggregates ismitochondria resulting inmitochondrial dysfunction
and increased oxidative stress. Nuclear factor (erythroid-derived 2)-like 2 and its Caenorhabditiselegans ortholog, SKN-1, are
transcription factors that have a pivotal role in the oxidative stress response, cellular homeostasis, and organismal lifespan.
Similar to other defense systems, the NRF2-mediated stress response is compromised in aging and neurodegenerative diseases.
Here, we report that the FDA approved drug hydralazine is a bona fide activator of the NRF2/SKN-1 signaling pathway. We
demonstrate that hydralazine extends healthy lifespan (~25%) in wild-type and tauopathy model
C. elegans
at least as effective
as other anti-aging compounds, such as curcumin and metformin. We show that hydralazine-mediated lifespan extension is
SKN-1 dependent, with a mechanism most likely mimicking calorie restriction. Using both
in vitro
and
in vivo
models, we
demonstrate that hydralazine has neuroprotective properties against endogenous and exogenous stressors. Our data suggest
that hydralazine may be a viable candidate for the treatment of age-related disorders.
Biography
Dr Hamid Mirzaei’s research is focused on finding the target of novel and FDA approved compounds using a combination of proteomics, computational biology, and
biochemistry. Many FDA approved drugs are currently in use without the clear understanding of their mechanism of action. On the other hand, there are quite a few
well-characterized natural products with unknown targets. Dr Mirzaei uses systems biology to understand the drug’s mechanism of action by identifying the target
of the drugs and their cellular and organismal phenotypes.
Hamid.Mirzaei@utsouthwestern.eduHamid Mirzaei
UT Southwestern Medical Center, USA
Hamid Mirzaei, J Glycobiol 2018, Volume 7
DOI: 10.4172/2168-958X-C1-010