[Frontiers in Bioscience S2, 359-372, January 1, 2010]

Homocysteine, vitamin determinants and neurological diseases

Riccardo Ientile1, Monica Curro'1, Nadia Ferlazzo1, Salvatore Condello1, Daniela Caccamo1, Francesco Pisani2

1Department of Biochemical, Physiological and Nutritional Sciences, University of Messina, Messina, Italy, 2Department of Neurosciences, Neurology Clinic, University of Messina, Messina, Italy

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Homocysteine metabolism
4. Genetic polymorphisms involved in homocysteine metabolism
5. Homocysteine -mediated mechanisms of toxicity in the nervous system
5.1. Excitotoxic effects
5.2. Oxidative effects
5.3. Inflammatory effects
6. Cerebrovascular disease
7. Cognitive impairment and Alzheimer's Disease
8. Parkinson's Disease
9. Epilepsy
10. Multiple sclerosis
11. Moving toward a different view: Homocysteine as an indicator of vitamin status
12. Conclusions and perspectives
13. Acknowledgements
14. References

1. ABSTRACT

This review focuses on the putative role of hyper-homocysteinemia in the pathogenesis of different diseases affecting the nervous system, including stroke, Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis and amyotrophic lateral sclerosis. However, a firm pathogenic role of homocysteine in these diseases has never been established. Lowering plasma homocysteine levels trough vitamin therapy failed to prevent vascular diseases. Conversely, normalization of hyper-homocysteinemia caused improvement in patients with cognitive impairment. B vitamin deficiency is the main determinant of homocysteine levels. However, it has been hypothesized that homocysteine might be a mere marker of vitamin deficiency or an indicator of disease rather than a risk factor. A more consistent use of thresholds to define deficiency is needed to recommend routine screening, monitoring and supplementation of B vitamins to ameliorate the prognosis of the above mentioned disorders. To date, data are insufficient to firmly establish which one of the hypotheses made is correct and the question concerning the real meaning of hyper-homocysteinemia in the pathology of the nervous system still remains an intriguing medical dilemma.