Homocysteine and Parkinson's disease: a dangerous liaison?
Homocysteine, a sulphur-containing amino acid formed by demethylation of methionine, is involved in numerous processes of methyl group transfer, all playing pivotal roles in the biochemistry of the human body. Increased levels of plasma homocysteine (hyperhomocysteinemia) - which may result from a deficiency of folate, vitamin B6 or B12 or mutations in enzymes regulating the catabolism of homocysteine - are associated with a wide range of clinical manifestations, mostly affecting the central nervous system (e.g., mental retardation, cerebral atrophy and epileptic seizures). Recent evidence suggests that changes in the metabolic fate of homocysteine, leading to hyperhomocysteinemia, may also play a role in the pathophysiology of neurodegenerative disorders, particularly Parkinson's disease (PD). The nervous system might be particularly sensitive to homocysteine, due to the excitotoxic-like properties of the amino acid. However, experimental findings have shown that homocysteine does not seem to posses direct, cytotoxic activity, while the amino acid has proven able to synergize with more specific neurotoxic insults. Hyperhomocysteinemia has been repeatedly reported in PD patients; the increase, however, seems mostly related to the methylated catabolism of l-Dopa, the main pharmacological treatment of PD. Therefore, hyperhomocysteinemia may not be specific to movement disorders or other neurological diseases, the condition being, in fact, rather the result of the combinations of different factors, mainly metabolic, but also genetic and pharmacological, intervening in the neurodegenerative process.
Martignoni
E
E
IRCCS S. Maugeri Foundation, Scientific Institute of Veruno, Via per Revislate 13, 28010 Veruno (NO), Italy. emilia.martignoni@libero.it
Tassorelli
C
C
Nappi
G
G
Zangaglia
R
R
Pacchetti
C
C
Blandini
F
F
D001921:Brain / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D001928:Brain Diseases, Metabolic / Q000150:complications / Q000503:physiopathology; D015984:Causality; D006710:Homocysteine / Q000378:metabolism*; D006801:Humans; D020138:Hyperhomocysteinemia / Q000150:complications* / Q000503:physiopathology; D007980:Levodopa / Q000378:metabolism; D009410:Nerve Degeneration / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D010300:Parkinson Disease / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology
D006710:Homocysteine; D007980:Levodopa