Abstract
An elevated concentration of total homocysteine (tHcy) in plasma and cerebrospinal fluid is considered to be a risk factor for Alzheimer's disease (AD) and Parkinson's disease (PD). Homocysteine (Hcy) levels are influenced by folate concentrations and numerous genetic factors through the folate cycle, however, their role in the pathogenesis of PD remains controversial. Hcy exerts a neurotoxic action and may participate in the mechanisms of neurodegeneration, such as excitotoxicity, oxidative stress, calcium accumulation, and apoptosis. Elevated Hcy levels can lead to prooxidative activity, most probably through direct interaction with N-methyl-D-aspartate (NMDA) receptors and sensitization of dopaminergic neurons to age-related dysfunction and death. Several studies have shown that higher concentration of Hcy in PD is related to long-term administration of levodopa (L-dopa). An elevation of plasma tHcy levels can also reflect deficiencies of cofactors in remethylation of Hcy to methionine (Met) (folates and vitamin B12) and in its transsulfuration to cysteine (Cys) (vitamin B6). It is believed that the increase in the concentration of Hcy in PD can affect genetic polymorphisms of the folate metabolic pathway genes, such as MTHFR (C677T, A1298C and G1793A), MTR (A2756G), and MTHFD1 (G1958A), whose frequencies tend to increase in PD patients, as well as the reduced concentration of B vitamins. In PD, increased levels of Hcy may lead to dementia, depression and progression of the disease.
Keywords: MTHFR, MTR, MTHFD1 polymorphism, Biothiols, PD.
Current Genomics
Title:Homocysteine Level and Mechanisms of Injury in Parkinson's Disease as Related to MTHFR, MTR, and MTHFD1 Genes Polymorphisms and LDopa Treatment
Volume: 14 Issue: 8
Author(s): Agata Rozycka, Pawel P. Jagodzinski, Wojciech Kozubski, Margarita Lianeri and Jolanta Dorszewska
Affiliation:
Keywords: MTHFR, MTR, MTHFD1 polymorphism, Biothiols, PD.
Abstract: An elevated concentration of total homocysteine (tHcy) in plasma and cerebrospinal fluid is considered to be a risk factor for Alzheimer's disease (AD) and Parkinson's disease (PD). Homocysteine (Hcy) levels are influenced by folate concentrations and numerous genetic factors through the folate cycle, however, their role in the pathogenesis of PD remains controversial. Hcy exerts a neurotoxic action and may participate in the mechanisms of neurodegeneration, such as excitotoxicity, oxidative stress, calcium accumulation, and apoptosis. Elevated Hcy levels can lead to prooxidative activity, most probably through direct interaction with N-methyl-D-aspartate (NMDA) receptors and sensitization of dopaminergic neurons to age-related dysfunction and death. Several studies have shown that higher concentration of Hcy in PD is related to long-term administration of levodopa (L-dopa). An elevation of plasma tHcy levels can also reflect deficiencies of cofactors in remethylation of Hcy to methionine (Met) (folates and vitamin B12) and in its transsulfuration to cysteine (Cys) (vitamin B6). It is believed that the increase in the concentration of Hcy in PD can affect genetic polymorphisms of the folate metabolic pathway genes, such as MTHFR (C677T, A1298C and G1793A), MTR (A2756G), and MTHFD1 (G1958A), whose frequencies tend to increase in PD patients, as well as the reduced concentration of B vitamins. In PD, increased levels of Hcy may lead to dementia, depression and progression of the disease.
Export Options
About this article
Cite this article as:
Rozycka Agata, Jagodzinski P. Pawel, Kozubski Wojciech, Lianeri Margarita and Dorszewska Jolanta, Homocysteine Level and Mechanisms of Injury in Parkinson's Disease as Related to MTHFR, MTR, and MTHFD1 Genes Polymorphisms and LDopa Treatment, Current Genomics 2013; 14 (8) . https://dx.doi.org/10.2174/1389202914666131210210559
DOI https://dx.doi.org/10.2174/1389202914666131210210559 |
Print ISSN 1389-2029 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5488 |
Call for Papers in Thematic Issues
Advanced AI Techniques in Big Genomic Data Analysis
The thematic issue on "Advanced AI Techniques in Big Genomic Data Analysis" aims to explore the cutting-edge methodologies and applications of artificial intelligence (AI) in the realm of genomic research, where vast amounts of data pose both challenges and opportunities. This issue will cover a broad spectrum of AI-driven strategies, ...read more
Advanced Computational Algorithms and Artificial Intelligence in Clinical Pharmacogenomics
In the era of personalized medicine, understanding the relationship between genetics and drug response is crucial. This issue delves into innovative methodologies, leveraging deep computational analysis and artificial intelligence, to enhance the field of Clinical Pharmacogenomics. The interdisciplinary approach harnesses the power of advanced high-throughput genotyping technologies, sophisticated computational analysis, ...read more
Applications of Single-cell Sequencing Technology in Reproductive Medicine
Single cell sequencing (SCS) technology utilizes individual cells' genetic material to sequence their genome, transcriptome, and epigenetics at the molecular level. It offers insights into cell heterogeneity and enables the study of limited biological materials. Since its recognition as a valuable technique in 2011, single cell sequencing has yielded numerous ...read more
Big Data in Cancer Research
Cancer is a significant threat to human life and health, remaining a highly aggressive killer. It is a leading cause of death worldwide and represents a crucial medical issue for humanity. However, in the past decade, the effectiveness of new synthetic anticancer agents has not matched the current clinical speculation. ...read more
Related Journals
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Dysregulated Pathway Identification of Alzheimer's Disease Based on Internal Correlation Analysis of Genes and Pathways
Combinatorial Chemistry & High Throughput Screening Topical and Transdermal Delivery of Drug-Loaded Nano/ Microsystems with Application of Physical Enhancement Techniques
Current Drug Targets Emerging Therapeutic Targets in Regenerative Medicine for the Treatment of Diabetes Mellitus: A Patent Literature Review
Recent Patents on Regenerative Medicine Clinical Molecular Imaging with PET Agents Other than 18F-FDG
Current Pharmaceutical Biotechnology Subject Index To Volume 8
Protein & Peptide Letters Hypersensitivity Reactions to Complementary and Alternative Medicine Products
Current Pharmaceutical Design Neuron-Specific Mitochondrial DNA Deletion Levels in Sporadic Alzheimer´s Disease
Current Alzheimer Research Molecular Modelling Studies on Thiazole-Based α-Glucosidase Inhibitors Using Docking and CoMFA, CoMSIA and HQSAR
Current Drug Discovery Technologies Dementia After Age 75: Survival in Different Severity Stages and Years of Life Lost
Current Alzheimer Research Subcellular Analysis of the Platelet Proteome
Current Proteomics Prognostic Significance of Homocysteine Levels in Acute Ischemic Stroke: A Prospective Cohort Study
Current Neurovascular Research Redox Processes in Neurodegenerative Disease Involving Reactive Oxygen Species
Current Neuropharmacology Neuronal Cell Death in Alzheimers Disease and a Neuroprotective Factor, Humanin
Current Neuropharmacology Functional Magnetic Resonance Imaging in Abstinent MDMA Users: A Review
Current Drug Abuse Reviews Amyloid Beta Protein and Tau in Cerebrospinal Fluid and Plasma as Biomarkers for Dementia: A Review of Recent Literature
Current Clinical Pharmacology Vasculogenic and Angiogenic Pathways in Moyamoya Disease
Current Medicinal Chemistry Nitric Oxide and Dietary Factors: Part V Summary/Conclusion and References
Vascular Disease Prevention (Discontinued) Schizophrenia: Causes and Treatments
Current Pharmaceutical Design Functional and Structural Benefits Induced by Omega-3 Polyunsaturated Fatty Acids During Aging
Current Neuropharmacology Quinoline Derivatives: Candidate Drugs for a Class B G-Protein Coupled Receptor, the Calcitonin Gene-Related Peptide Receptor, a Cause of Migraines
CNS & Neurological Disorders - Drug Targets