The Imbalance of Homocysteine, Vitamin B12 and Folic Acid in Parkinson Plus Syndromes: A Review beyond Parkinson Disease

Abstract

While there is a link between homocysteine (Hcy), B12 and folic acid and neurodegeneration, especially in disorders like Parkinson's and Alzheimer's diseases, its role in Parkinson plus syndromes (PPS) has only been partially investigated. It appears that elevated Hcy, along with an imbalance of its essential vitamin cofactors, are both implicated in the development and progression of parkinsonian syndromes, which represent different disease pathologies, namely alpha-synucleinopathies and tauopathies. Attributing a potential pathogenetic role in hyperhomocysteinemia would be crucial in terms of improving the diagnostic and prognostic accuracy of these syndromes and also for providing a new target for possible therapeutic intervention. The scope of this review is to focus on vitamin imbalance in PPS, with a special emphasis on the role of Hcy, B12 and folic acid in the neurodegenerative process and their implication in the therapeutic approach of these disorders.

Keywords: Parkinson plus syndromes; alpha-synuclein; folate; homocysteine; tau protein; vitamin B12.

Figure 1

Hcy metabolism is mediated by vitamin cofactors. HHcy can facilitate the pathological accumulation of α-synuclein and increase the levels of phosphorylated tau.