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
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
Current Genomics in Cardiovascular Research
Cardiovascular diseases are the main cause of death in the world, in recent years we have had important advances in the interaction between cardiovascular disease and genomics. In this Research Topic, we intend for researchers to present their results with a focus on basic, translational and clinical investigations associated with ...read more
Deep learning in Single Cell Analysis
The field of biology is undergoing a revolution in our ability to study individual cells at the molecular level, and to integrate data from multiple sources and modalities. This has been made possible by advances in technologies for single-cell sequencing, multi-omics profiling, spatial transcriptomics, and high-throughput imaging, as well as ...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
-
Tailored Multi-Target Agents. Applications and Design Considerations
Current Pharmaceutical Design Neuroimaging Outcomes in Studies of Cognitive Training in Mild Cognitive Impairment and Early Alzheimer’s Disease: A Systematic Review
Current Alzheimer Research Enriching One’s Environment in the Face of Cognitive and Functional Loss
Current Neurovascular Research Artery of Percheron Infarction: A Characteristic Pattern of Ischemia and Variable Clinical Presentation: A Literature Review
Current Medical Imaging Antithrombotic Treatment in the Prevention of Ischemic Stroke
Current Drug Targets Evaluation on Monocyte-Mediated Delivery of a Therapeutic Gene into the Inflamed Brain
Current Gene Therapy Glucocorticoids and the Cardiovascular System: State of the Art
Current Pharmaceutical Design Neural and Behavioral Responses to Systemic Immunologic Stimuli: A Consideration of Bacterial T Cell Superantigens
Current Pharmaceutical Design The Potential Role of Sirtuins Regarding the Effects of Exercise on Aging- Related Diseases
Current Aging Science Lifelong Endocrine Fluctuations and Related Cognitive Disorders
Current Pharmaceutical Design Metacognition and Social Functioning in Schizophrenia: Evidence, Mechanisms of Influence and Treatment Implications
Current Psychiatry Reviews Dietary Patterns and Cognitive Decline: key features for prevention
Current Pharmaceutical Design Epigenetics in Alzheimers Disease: a Focus on DNA Modifications
Current Pharmaceutical Design Adrenomedullin Function in Vascular Endothelial Cells: Insights from Genetic Mouse Models
Current Hypertension Reviews Early Life Stress in Depressive Patients: Role of Glucocorticoid and Mineralocorticoid Receptors and of Hypothalamic-Pituitary-Adrenal Axis Activity
Current Pharmaceutical Design Inflammatory Process as a Determinant Factor for the Degeneration of Substantia Nigra Dopaminergic Neurons: Possible Relevance to the Etiology of Parkinsons Disease
Current Medicinal Chemistry - Central Nervous System Agents Small Molecules that Promote Neurogenesis in vitro
Recent Patents on CNS Drug Discovery (Discontinued) Role of Vitamins in Human Health and Nutrition: Sources and Morbidity
Current Nutrition & Food Science PET Tracers for Mapping Adenosine Receptors as Probes for Diagnosis of CNS Disorders
Central Nervous System Agents in Medicinal Chemistry A Review of the Carbapenems in Clinical Use and Clinical Trials
Recent Patents on Anti-Infective Drug Discovery