Modeling neurodegenerative disease pathophysiology in thiamine deficiency: consequences of impaired oxidative metabolism

Neurochem Int. 2011 Feb;58(3):248-60. doi: 10.1016/j.neuint.2010.11.019. Epub 2010 Dec 3.

Abstract

Emerging evidence suggests that thiamine deficiency (TD), the cause of Wernicke's encephalopathy, produces alterations in brain function and structural damage that closely model a number of maladies in which neurodegeneration is a characteristic feature, including Alzheimer's disease, amyotrophic lateral sclerosis, Parkinson's disease, multiple sclerosis, along with alcoholic brain disease, stroke, and traumatic brain injury. Impaired oxidative metabolism in TD due to decreased activity of thiamine-dependent enzymes leads to a multifactorial cascade of events in the brain that include focal decreases in energy status, oxidative stress, lactic acidosis, blood-brain barrier disruption, astrocyte dysfunction, glutamate-mediated excitotoxicity, amyloid deposition, decreased glucose utilization, immediate-early gene induction, and inflammation. This review describes our current understanding of the basis of these abnormal processes in TD, their interrelationships, and why this disorder can be useful for our understanding of how decreased cerebral energy metabolism can give rise to cell death in different neurodegenerative disease states.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Energy Metabolism / physiology*
  • Humans
  • Neurodegenerative Diseases / etiology
  • Neurodegenerative Diseases / metabolism*
  • Neurodegenerative Diseases / physiopathology
  • Oxidation-Reduction
  • Oxidative Phosphorylation / drug effects
  • Thiamine / metabolism*
  • Thiamine Deficiency / complications
  • Thiamine Deficiency / metabolism*
  • Thiamine Deficiency / physiopathology

Substances

  • Thiamine