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little dab

a little dab’ll do ya

a little dab’ll do ya

a little dab’ll do ya

a little dab will do you

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Definition of a little dab'll do ya in the Idioms Dictionary. a little dab'll do ya phrase. What does a little dab'll do ya expression mean? Definitions by the largest Idiom Dictionary.

DNP, mitochondrial uncoupling, and neuroprotection: A little dab’ll do ya

Affiliations

  • 1 Mitochon Pharmaceuticals, Inc., Radnor, PA, USA.
  • 2 Laboratory of Neurosciences, National Institute on Aging Intramural Research Program, Baltimore, MD, USA.
  • 3 Laboratory of Neurosciences, National Institute on Aging Intramural Research Program, Baltimore, MD, USA; Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address: [email protected]
  • PMID: 27599210
  • PMCID: PMC5337177
  • DOI: 10.1016/j.jalz.2016.08.001
Free PMC article

DNP, mitochondrial uncoupling, and neuroprotection: A little dab’ll do ya

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Authors

Affiliations

  • 1 Mitochon Pharmaceuticals, Inc., Radnor, PA, USA.
  • 2 Laboratory of Neurosciences, National Institute on Aging Intramural Research Program, Baltimore, MD, USA.
  • 3 Laboratory of Neurosciences, National Institute on Aging Intramural Research Program, Baltimore, MD, USA; Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address: [email protected]
  • PMID: 27599210
  • PMCID: PMC5337177
  • DOI: 10.1016/j.jalz.2016.08.001

Abstract

Recent findings have elucidated roles for mitochondrial uncoupling proteins (UCPs) in neuronal plasticity and resistance to metabolic and oxidative stress. UCPs are induced by bioenergetic challenges such as caloric restriction and exercise and may protect neurons against dysfunction and degeneration. The pharmacological uncoupler 2,4-dinitrophenol (DNP), which was once prescribed to >100,000 people as a treatment for obesity, stimulates several adaptive cellular stress-response signaling pathways in neurons including those involving the brain-derived neurotrophic factor (BDNF), the transcription factor cyclic AMP response element-binding protein (CREB), and autophagy. Preclinical data show that low doses of DNP can protect neurons and improve functional outcome in animal models of Alzheimer’s and Parkinson’s diseases, epilepsy, and cerebral ischemic stroke. Repurposing of DNP and the development of novel uncoupling agents with hormetic mechanisms of action provide opportunities for new breakthrough therapeutic interventions in a range of acute and chronic insidious neurodegenerative/neuromuscular conditions, all paradoxically at body weight-preserving doses.

Keywords: BDNF; CREB; DNP; Hormesis; Mitochondrial uncoupling; Parkinson’s disease; Synaptic plasticity.

Published by Elsevier Inc.

Figures

Neuronal responses to mitochondrial uncoupling…

Neuronal responses to mitochondrial uncoupling are consistent with a hormesis-based mechanism of action.…

Mechanisms by which mild mitochondrial…

Mechanisms by which mild mitochondrial uncoupling protects neurons against oxidative stress, excitotoxicity and…

Treatment of mice with low…

Treatment of mice with low doses of the uncoupler DNP results in increased…

Historical timeline of studies of…

Historical timeline of studies of DNP dose-dependent clinical efficacy and toxicity, mechanisms of…

Recent findings have elucidated roles for mitochondrial uncoupling proteins (UCPs) in neuronal plasticity and resistance to metabolic and oxidative stress. UCPs are induced by bioenergetic challenges such as caloric restriction and exercise and may protect neurons against dysfunction and degeneratio … ]]>