Mechanisms of homocysteine neurotoxicity in neurodegenerative diseases with special reference to dementia

Mild to moderate hyperhomocysteinemia is a risk factor for neurodegenerative diseases. Human studies suggest that homocysteine (Hey) plays a role in brain damage, cognitive and memory decline. Numerous studies in recent years investigated the role of Hey as a cause of brain damage. Hey itself or folate and vitamin B12 deficiency can cause disturbed methylation and/or redox potentials, thus promoting calcium influx, amyloid and tau protein accumulation, apoptosis, and neuronal death. The Hey effect may also be mediated by activating the N-methyl-D-aspartate receptor subtype. Numerous neurotoxic, effects of Hey can be blocked by folate, glutamate receptor antagonists, or various antioxidants. This review describes the most important mechanisms of Hey neurotoxicity and pharmacological agents known to reverse Hey effects. (c) 2006 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.