Hyperhomocysteinemia in movement disorders: Current evidence and hypotheses

Curr Vasc Pharmacol. 2006 Jul;4(3):237-43. doi: 10.2174/157016106777698414.

Abstract

Elevated plasma levels of homocysteine (Hcy) are a risk factor for systemic vascular diseases, stroke and vascular dementia. In recent years, increasing Hcy levels have been detected in neurological disorders that are not vascular in origin including Alzheimer's Disease and movement disorders (MD) such as idiopathic Parkinson's Disease (PD), Huntington's Disease (HD) and primary dystonia. Hyperhomocysteinemia (HHcy) in PD results from L-Dopa administration and its O-methylation dependent from catechol-O-methyltransferase and may be implicated in the development of motor complications and non-motor symptoms, such as dementia. In a recent study, HHcy has been evidenced in HD patients, compared to controls. Because mutated Huntington protein influences Hcy metabolism by modulating cystathionine-beta-synthase activity, Hcy could represent a biological marker of neurodegeneration and could explain the leading role of cardiovascular and cerebrovascular diseases as causes of death in HD. Finally, several cases of homocystinuria associated with dystonia, and some recent reports of elevated Hcy in patients with primary adult onset dystonia have been published. Increased Hcy plasma levels may have important implications in patients affected by these basal ganglia disturbances, by exerting neurotoxic effects, contributing to neurotransmitter imbalance in motor circuits, and increasing the risk for vascular insults and cognitive dysfunctions.

Publication types

  • Meta-Analysis

MeSH terms

  • Adolescent
  • Adult
  • Animals
  • Case-Control Studies
  • Catechol O-Methyltransferase / metabolism
  • Cystathionine beta-Synthase / metabolism
  • Dopamine Agents / adverse effects
  • Dopamine Agents / metabolism
  • Dystonia / blood
  • Homocysteine / blood*
  • Homocysteine / metabolism
  • Humans
  • Huntington Disease / blood
  • Huntington Disease / enzymology
  • Hyperhomocysteinemia / blood*
  • Hyperhomocysteinemia / etiology
  • Hyperhomocysteinemia / metabolism
  • Levodopa / adverse effects
  • Levodopa / metabolism
  • Methylenetetrahydrofolate Reductase (NADPH2) / metabolism
  • Middle Aged
  • Movement Disorders / blood*
  • Movement Disorders / drug therapy
  • Movement Disorders / enzymology
  • Parkinson Disease / blood
  • Parkinson Disease / drug therapy
  • Parkinson Disease / enzymology
  • Prospective Studies

Substances

  • Dopamine Agents
  • Homocysteine
  • Levodopa
  • Methylenetetrahydrofolate Reductase (NADPH2)
  • Catechol O-Methyltransferase
  • Cystathionine beta-Synthase