Role of Homocysteine in the Development and Progression of Parkinson's Disease

Overview

Journal Ann Clin Transl Neurol

Specialty Neurology

Date 2020 Oct 21

PMID 33085841

Citations 37

Authors

Xiaoyan Fan

Lixia Zhang

Haijun Li

Guang Chen

Gangqiao Qi

Xueqiang Ma

Yuelei Jin

Affiliations

Soon will be listed here.

Abstract

Homocysteine is an essential intermediate product of biochemical reactions that is present in various tissues of the human body. Homocysteine may be associated with the development and progression of Parkinson's disease. Plasma homocysteine levels in patients with Parkinson's disease are elevated compared to those of healthy individuals. High homocysteine drives PD development and progression while aggregating the clinical symptoms of PD patients. The relationship between PD and homocysteine involves multiple pathways, including nerve cell apoptosis, oxidative stress, and DNA damage. This is crucial for explaining how high homocysteine drives the PD procession. Elevated homocysteine level during PD development and progression offers a new strategy for the diagnosis and treatment of this disease.

Citing Articles

Parkin characteristics and blood biomarkers of Parkinson's disease in WPBLC study.

He H, Xiong X, Zheng Y, Hou J, Jiang T, Quan W Front Aging Neurosci. 2025; 17:1511272.

PMID: 40078640 PMC: 11897490. DOI: 10.3389/fnagi.2025.1511272.

Multi-omics characterization of improved cognitive functions in Parkinson's disease patients after the combined metabolic activator treatment: a randomized, double-blinded, placebo-controlled phase II trial.

Yulug B, Altay O, Li X, Hanoglu L, Cankaya S, Velioglu H Brain Commun. 2025; 7(1):fcae478.

PMID: 39816194 PMC: 11733689. DOI: 10.1093/braincomms/fcae478.

Space exploration and risk of Parkinson's disease: a perspective review.

Ali N, Beheshti A, Hampikian G NPJ Microgravity. 2025; 11(1):1.

PMID: 39753605 PMC: 11698718. DOI: 10.1038/s41526-024-00457-6.

Safety, Tolerability and Pharmacokinetic-Pharmacodynamic Relationship of NX210c Peptide in Healthy Elderly Volunteers: Randomized, Placebo-Controlled, Double-Blind, Multiple Ascending Dose Study.

Janus A, Dumas D, Le Douce J, Marie S, Pasculli G, Bambury P Neurol Ther. 2024; 14(1):357-377.

PMID: 39708220 PMC: 11762061. DOI: 10.1007/s40120-024-00691-w.

Exploring the causal link between serum amino acids and Parkinson's disease: a Mendelian randomization approach.

Cheng L, Yan J, Shi W, Zhang J, Dong Q, Hu Y Sci Rep. 2024; 14(1):30271.

PMID: 39632961 PMC: 11618358. DOI: 10.1038/s41598-024-81787-z.

References

Martinez Y, Li X, Liu G, Bin P, Yan W, Mas D . The role of methionine on metabolism, oxidative stress, and diseases. Amino Acids. 2017; 49(12):2091-2098. DOI: 10.1007/s00726-017-2494-2. View

Kalra D . Homocysteine and cardiovascular disease. Curr Atheroscler Rep. 2004; 6(2):101-6. DOI: 10.1007/s11883-004-0097-3. View

Constans J, Blann A, Resplandy F, Parrot F, Seigneur M, Renard M . Endothelial dysfunction during acute methionine load in hyperhomocysteinaemic patients. Atherosclerosis. 1999; 147(2):411-3. DOI: 10.1016/s0021-9150(99)00260-9. View

Gudnason V, Stansbie D, Scott J, Bowron A, Nicaud V, Humphries S . C677T (thermolabile alanine/valine) polymorphism in methylenetetrahydrofolate reductase (MTHFR): its frequency and impact on plasma homocysteine concentration in different European populations. EARS group. Atherosclerosis. 1998; 136(2):347-54. DOI: 10.1016/s0021-9150(97)00237-2. View

Streck E, Matte C, Vieira P, Calcagnotto T, Wannmacher C, Wajner M . Impairment of energy metabolism in hippocampus of rats subjected to chemically-induced hyperhomocysteinemia. Biochim Biophys Acta. 2003; 1637(3):187-92. DOI: 10.1016/s0925-4439(03)00019-x. View

Wollesen F, Brattstrom L, Refsum H, Ueland P, Berglund L, Berne C . Plasma total homocysteine and cysteine in relation to glomerular filtration rate in diabetes mellitus. Kidney Int. 1999; 55(3):1028-35. DOI: 10.1046/j.1523-1755.1999.0550031028.x. View

Postuma R, Berg D, Stern M, Poewe W, Olanow C, Oertel W . MDS clinical diagnostic criteria for Parkinson's disease. Mov Disord. 2015; 30(12):1591-601. DOI: 10.1002/mds.26424. View

Selhub J, Jacques P, Wilson P, Rush D, Rosenberg I . Vitamin status and intake as primary determinants of homocysteinemia in an elderly population. JAMA. 1993; 270(22):2693-8. DOI: 10.1001/jama.1993.03510220049033. View

De Virgilio A, Greco A, Fabbrini G, Inghilleri M, Rizzo M, Gallo A . Corrigendum to "Parkinson's disease: Autoimmunity and neuroinflammation" [Autoimmun Rev 15 (10) (2016) 1005-1011]. Autoimmun Rev. 2016; 15(12):1210. DOI: 10.1016/j.autrev.2016.09.027. View

10.

dos Santos E, Busanello E, Miglioranza A, Zanatta A, Barchak A, Vargas C . Evidence that folic acid deficiency is a major determinant of hyperhomocysteinemia in Parkinson's disease. Metab Brain Dis. 2009; 24(2):257-69. DOI: 10.1007/s11011-009-9139-4. View

11.

Skovierova H, Vidomanova E, Mahmood S, Sopkova J, Drgova A, cervenova T . The Molecular and Cellular Effect of Homocysteine Metabolism Imbalance on Human Health. Int J Mol Sci. 2016; 17(10). PMC: 5085763. DOI: 10.3390/ijms17101733. View

12.

Hasan T, Arora R, Bansal A, Bhattacharya R, Sharma G, Singh L . Disturbed homocysteine metabolism is associated with cancer. Exp Mol Med. 2019; 51(2):1-13. PMC: 6389897. DOI: 10.1038/s12276-019-0216-4. View

13.

Duan W, Ladenheim B, Cutler R, Kruman I, Cadet J, Mattson M . Dietary folate deficiency and elevated homocysteine levels endanger dopaminergic neurons in models of Parkinson's disease. J Neurochem. 2002; 80(1):101-10. DOI: 10.1046/j.0022-3042.2001.00676.x. View

14.

Mudd S, EBERT M, Scriver C . Labile methyl group balances in the human: the role of sarcosine. Metabolism. 1980; 29(8):707-20. DOI: 10.1016/0026-0495(80)90192-4. View

15.

Ueland P, Refsum H, Stabler S, MALINOW M, Andersson A, Allen R . Total homocysteine in plasma or serum: methods and clinical applications. Clin Chem. 1993; 39(9):1764-79. View

16.

Kim Y . Folate and DNA methylation: a mechanistic link between folate deficiency and colorectal cancer?. Cancer Epidemiol Biomarkers Prev. 2004; 13(4):511-9. View

17.

Kim W, Pae Y . Involvement of N-methyl-d-aspartate receptor and free radical in homocysteine-mediated toxicity on rat cerebellar granule cells in culture. Neurosci Lett. 1996; 216(2):117-20. DOI: 10.1016/0304-3940(96)13011-1. View

18.

Dekou V, Whincup P, Papacosta O, Ebrahim S, Lennon L, Ueland P . The effect of the C677T and A1298C polymorphisms in the methylenetetrahydrofolate reductase gene on homocysteine levels in elderly men and women from the British regional heart study. Atherosclerosis. 2001; 154(3):659-66. DOI: 10.1016/s0021-9150(00)00522-0. View

19.

Varani J, Dame M, Taylor C, Sarma V, Merino R, Kunkel R . Age-dependent injury in human umbilical vein endothelial cells: relationship to apoptosis and correlation with a lack of A20 expression. Lab Invest. 1995; 73(6):851-8. View

20.

Mudd S, Skovby F, Levy H, Pettigrew K, Wilcken B, Pyeritz R . The natural history of homocystinuria due to cystathionine beta-synthase deficiency. Am J Hum Genet. 1985; 37(1):1-31. PMC: 1684548. View