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
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
New insights on Pediatric Tumors and Associated Cancer Predisposition Syndromes
Because of the broad spectrum of children cancer susceptibility, the diagnosis of cancer risk syndromes in children is rarely used in direct cancer treatment. The field of pediatric cancer genetics and genomics will only continue to expand as a result of increasing use of genetic testing tools. It's possible that ...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
-
“SLY AS A FOXO”: New Paths with Forkhead Signaling in the Brain
Current Neurovascular Research Genetic Editing and Pharmacogenetics in Current And Future Therapy Of Neurocognitive Disorders
Current Alzheimer Research Adiponectin and its Role in Cardiovascular Diseases
Cardiovascular & Hematological Disorders-Drug Targets Cognitive Decline as a Consequence of Essential Hypertension
Current Pharmaceutical Design Cognitive Impairment Associated with Parkinson’s Disease: Role of Mitochondria
Current Neuropharmacology Classification of Acetylcholinesterase Inhibitors and Decoys by a Support Vector Machine
Combinatorial Chemistry & High Throughput Screening Synthesis, Molecular Docking and Antiamnesic Activity of Selected 2- Naphthyloxy Derivatives
Medicinal Chemistry HIV and Substance Abuse: A Commentary
Current HIV Research Therapeutic Effects of Quetiapine on Memory Deficit and Brain β-Amyloid Plaque Pathology in a Transgenic Mouse Model of Alzheimer’s Disease
Current Alzheimer Research Meet Our Associate Editor
Current Alzheimer Research Forkhead Transcription Factors: Formulating a FOXO Target for Cognitive Loss
Current Neurovascular Research The Prevalence of Frailty in Patients Admitted to Hospital with Vertebral Fragility Fractures
Current Rheumatology Reviews Depression and Anxiety Levels Increase Chronic Musculoskeletal Pain in Patients with Alzheimer's Disease
Current Alzheimer Research Blood Platelet Reactivity and its Pharmacological Modulation in (People with) Diabetes Mellitus
Current Pharmaceutical Design Geriatric Evaluation of Oncological Elderly Patients
Anti-Cancer Agents in Medicinal Chemistry Selectivity Problems with Drugs Acting on Cardiac Na<sup>+</sup> and Ca<sup>2+</sup> Channels
Current Medicinal Chemistry Neuroprotective Effects of Lithium in Human Brain? Food for Thought
Current Alzheimer Research Spatial Correlations between the Vacuolation, Prion Protein (PrPsc) Deposits and the Cerebral Blood Vessels in Sporadic Creutzfeldt-Jakob Disease
Current Neurovascular Research Study of the Effects of L-tryptophane Nanoparticles on Motor Behavior in Alzheimer's Experimental Models
CNS & Neurological Disorders - Drug Targets Apolipoprotein E Knockout Models
Current Pharmaceutical Design