Abstract
Background: Homocysteine (Hcy) exerts multiple neurotoxic mechanisms that have been linked to the pathogenesis of neurodegenerative disorders. Several studies observed elevated plasma Hcy levels in Parkinsons Disease (PD) patients treated with L-dopa, compared to healthy controls and to patients with other neurodegenetative disorders. Objective: We performed an overview of published evidences assessing the possible correlations between Hcy levels and the incidence or pathogenesis of PD. Methods: A Medline literature search was performed to identify all available studies on Hcy and the incidence or pathophysiology of PD up to 30/09/2009. Results: 30 studies were included in this overview (20 studies on humans, 10 experimental studies). The relationship between metilentetrahydrofolate-reductase genotype (the most common genetic cause of hyperhomocysteinemia) and the development of PD was contradictory. Dietary patterns and B-vitamins levels (important determinants of Hcy levels) were associated with a not-significant increased risk of PD in three prospective studies. Investigations on plasma and cerebrospinalfluid Hcy concentrations in L-dopa naive PD patients gave conflicting results; some studies observed increased Hcy levels in L-dopa naive PD patients compared to controls, while others found no difference. In vitro, Hcy caused dosedependent depletion of dopaminergic mesencephalic neurons, by numerous pathogenetic mechanisms. In vivo brain administration of Hcy induced motor and behavioural changes, similar to those observed in animal models of PD. Conclusions: Based on the available data, the possibility that the hyperhomocysteinemia may contribute to the pathogenesis of PD remains uncertain. L-dopa treatment represents the major determinant of the hyperhomocysteinemia observed in PD.
Keywords: Parkinson's Disease, Homocysteine (Hcy), neurotoxic mechanisms, pathogenesis, L-dopa
Current Medicinal Chemistry
Title: Elevated Homocysteine Levels in Parkinsons Disease: Is there Anything Besides L-Dopa Treatment?
Volume: 17 Issue: 3
Author(s): S. Zoccolella, C. dell'Aquila, L. M. Specchio, G. Logroscino and P. Lamberti
Affiliation:
Keywords: Parkinson's Disease, Homocysteine (Hcy), neurotoxic mechanisms, pathogenesis, L-dopa
Abstract: Background: Homocysteine (Hcy) exerts multiple neurotoxic mechanisms that have been linked to the pathogenesis of neurodegenerative disorders. Several studies observed elevated plasma Hcy levels in Parkinsons Disease (PD) patients treated with L-dopa, compared to healthy controls and to patients with other neurodegenetative disorders. Objective: We performed an overview of published evidences assessing the possible correlations between Hcy levels and the incidence or pathogenesis of PD. Methods: A Medline literature search was performed to identify all available studies on Hcy and the incidence or pathophysiology of PD up to 30/09/2009. Results: 30 studies were included in this overview (20 studies on humans, 10 experimental studies). The relationship between metilentetrahydrofolate-reductase genotype (the most common genetic cause of hyperhomocysteinemia) and the development of PD was contradictory. Dietary patterns and B-vitamins levels (important determinants of Hcy levels) were associated with a not-significant increased risk of PD in three prospective studies. Investigations on plasma and cerebrospinalfluid Hcy concentrations in L-dopa naive PD patients gave conflicting results; some studies observed increased Hcy levels in L-dopa naive PD patients compared to controls, while others found no difference. In vitro, Hcy caused dosedependent depletion of dopaminergic mesencephalic neurons, by numerous pathogenetic mechanisms. In vivo brain administration of Hcy induced motor and behavioural changes, similar to those observed in animal models of PD. Conclusions: Based on the available data, the possibility that the hyperhomocysteinemia may contribute to the pathogenesis of PD remains uncertain. L-dopa treatment represents the major determinant of the hyperhomocysteinemia observed in PD.
Export Options
About this article
Cite this article as:
Zoccolella S., dell'Aquila C., Specchio M. L., Logroscino G. and Lamberti P., Elevated Homocysteine Levels in Parkinsons Disease: Is there Anything Besides L-Dopa Treatment?, Current Medicinal Chemistry 2010; 17 (3) . https://dx.doi.org/10.2174/092986710790149774
DOI https://dx.doi.org/10.2174/092986710790149774 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...read more
- 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
-
The Glutamatergic Hypothesis for Down Syndrome: The Potential Use of N-Methyl-D-Aspartate Receptor Antagonists to Enhance Cognition and Decelerate Neurodegeneration
CNS & Neurological Disorders - Drug Targets Dysregulation of RNA Mediated Gene Expression in Motor Neuron Diseases
CNS & Neurological Disorders - Drug Targets Transglutaminase-Catalyzed Crosslinking in Neurological Disease: From Experimental Evidence to Therapeutic Inhibition
CNS & Neurological Disorders - Drug Targets Structural and Molecular Basis of Carbohydrate-Protein Interaction Systems as Potential Therapeutic Targets
Current Pharmaceutical Design Systemic DNA Damage Response and Metabolic Syndrome as a Premalignant State
Current Molecular Medicine Introduction: Strategies, Molecular Targets and Animal Models Useful for Developing Therapies for Alzheimers Disease
Current Medicinal Chemistry - Central Nervous System Agents Potential Therapeutic Approaches to Alzheimer’s Disease By Bioinformatics, Cheminformatics And Predicted Adme-Tox Tools
Current Neuropharmacology Multi- and Inter-Disciplinary Science in Personalized Delivery of Stem Cells for Tissue Repair
Current Stem Cell Research & Therapy Bone Marrow-Derived Mesenchymal Stem Cells Contribute to the Reduction of Amyloid-β Deposits and the Improvement of Synaptic Transmission in a Mouse Model of Pre-Dementia Alzheimer’s Disease
Current Alzheimer Research Omega-3 Fatty Acids as Druggable Therapeutics for Neurodegenerative Disorders
CNS & Neurological Disorders - Drug Targets Opioids Resistance in Chronic Pain Management
Current Neuropharmacology Modulation of Endoplasmic Reticulum Stress: An Opportunity to Prevent Neurodegeneration?
CNS & Neurological Disorders - Drug Targets Meet Our Editorial Board Member
CNS & Neurological Disorders - Drug Targets How and When Environmental Agents and Dietary Factors Affect the Course of Alzheimers Disease: The “LEARn” Model (Latent Early-Life Associated Regulation) May Explain the Triggering of AD
Current Alzheimer Research The Role of the Endoplasmic Reticulum in the Accumulation of β-Amyloid Peptide in Alzheimers Disease
Current Molecular Medicine Nanowired Drug Delivery of Antioxidant Compound H-290/51 Enhances Neuroprotection in Hyperthermia-Induced Neurotoxicity
CNS & Neurological Disorders - Drug Targets Nicotinic Receptors in Neurodegeneration
Current Neuropharmacology Brain Functional Effects of Psychopharmacological Treatments in Schizophrenia: A Network-based Functional Perspective Beyond Neurotransmitter Systems
Current Neuropharmacology Meet Our Editorial Board Member
Current Psychiatry Reviews Antioxidants and its Properties as Affected by Extrusion Process: A Review
Recent Patents on Food, Nutrition & Agriculture