Management of the aging risk factor for Parkinson's disease

Neurobiol Aging. 2014 Apr;35(4):847-57. doi: 10.1016/j.neurobiolaging.2013.10.073. Epub 2013 Oct 10.

Abstract

The aging risk factor for Parkinson's disease is described in terms of specific disease markers including mitochondrial and gene dysfunctions relevant to energy metabolism. This review details evidence for the ability of nutritional agents to manage these aging risk factors. The combination of alpha lipoic acid, acetyl-l-carnitine, coenzyme Q10, and melatonin supports energy metabolism via carbohydrate and fatty acid utilization, assists electron transport and adenosine triphosphate synthesis, counters oxidative and nitrosative stress, and raises defenses against protein misfolding, inflammatory stimuli, iron, and other endogenous or xenobiotic toxins. These effects are supported by gene expression via the antioxidant response element (ARE; Keap/Nrf2 pathway), and by peroxisome proliferator-activated receptor gamma co-activator 1 alpha (PGC-1 alpha), a transcription coactivator, which regulates gene expression for energy metabolism and mitochondrial biogenesis, and maintains the structural integrity of mitochondria. The effectiveness and synergies of the combination against disease risks are discussed in relation to gene action, dopamine cell loss, and the accumulation and spread of pathology via misfolded alpha-synuclein. In addition there are potential synergies to support a neurorestorative role via glial derived neurotrophic factor expression.

Keywords: Acetyl-l-carnitine; Aging; Alpha lipoic acid; Coenzyme Q10; Melatonin; Mitochondria; Nrf2; PGC-1alpha; Parkinson's disease.

Publication types

  • Review

MeSH terms

  • Acetylcarnitine / administration & dosage
  • Acetylcarnitine / physiology
  • Adenosine Triphosphate / biosynthesis
  • Aging*
  • Antioxidant Response Elements
  • Carbohydrate Metabolism
  • Electron Transport
  • Energy Metabolism / genetics
  • Fatty Acids / metabolism
  • Glial Cell Line-Derived Neurotrophic Factor / physiology
  • Humans
  • Inflammation / prevention & control
  • Melatonin / administration & dosage
  • Melatonin / physiology
  • Mitochondria / genetics
  • Nitric Oxide / physiology
  • Oxidative Stress
  • Parkinson Disease / etiology*
  • Parkinson Disease / genetics
  • Parkinson Disease / prevention & control*
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Proteostasis Deficiencies / prevention & control
  • Risk Factors
  • Thioctic Acid / administration & dosage
  • Thioctic Acid / physiology
  • Transcription Factors
  • Ubiquinone / administration & dosage
  • Ubiquinone / analogs & derivatives
  • Ubiquinone / physiology
  • alpha-Synuclein

Substances

  • Fatty Acids
  • Glial Cell Line-Derived Neurotrophic Factor
  • PPARGC1A protein, human
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Transcription Factors
  • alpha-Synuclein
  • Ubiquinone
  • Nitric Oxide
  • Acetylcarnitine
  • Thioctic Acid
  • Adenosine Triphosphate
  • coenzyme Q10
  • Melatonin