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
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
Current advances in inherited cardiomyopathy
Describe in detail all novel advances in multimodality imaging related to inherited cardiomyopathy diagnosis and prognosis. Shed light to deeper phenotypic characterization. Acknowledge recent advances in genetics, genomics and precision medicineread 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
-
Editorial (BIOQUEST India: A Global Biotechnology Forum for Knowledge-Based Innovation and Sustainable Development)
Current Pharmacogenomics and Personalized Medicine Brain Oxidative Stress in Animal Models of Accelerated Aging and the Age-related Neurodegenerative Disorders, Alzheimers Disease and Huntingtons Disease
Current Medicinal Chemistry Good Epidemiologic Practice in Retinitis Pigmentosa: From Phenotyping to Biobanking
Current Genomics Chelating Agents for Neurodegenerative Diseases
Current Medicinal Chemistry In Vitro and In Vivo Models of Multiple Sclerosis
CNS & Neurological Disorders - Drug Targets Computational Approaches for Translational Oncology: Concepts and Patents
Recent Patents on Anti-Cancer Drug Discovery Glitazones, PPAR-γ and Neuroprotection
Mini-Reviews in Medicinal Chemistry Involvement of the Septo-Hippocampal Cholinergic Pathway in Association with Septal Acetylcholinesterase Upregulation in a Mouse Model of Tauopathy
Current Alzheimer Research Synthesis of Novel 4-(Dimethylaminoalkyl)piperazine-1-carbodithioa t e Derivatives as Cholinesterase Inhibitors
Letters in Drug Design & Discovery Editorial [Hot Topic: Bringing Drugs Into the Injured Brain and Keeping Them There (Executive Guest Editors: Dirk M. Hermann and Pauline Patak)]
Current Pharmaceutical Design Cross-Talk Between NO Synthase Isoforms in Neuro-Inflammation: Possible Implications in HIV-Associated Neurocognitive Disorders
Current Medicinal Chemistry Development of a Novel and Robust Pharmacological Model of Okadaic Acid-induced Alzheimer’s Disease in Zebrafish
CNS & Neurological Disorders - Drug Targets Reactive Astrogliosis: Role in Alzheimer's Disease
CNS & Neurological Disorders - Drug Targets Brain Senescence and Neuroprotective Dietary Components
Central Nervous System Agents in Medicinal Chemistry Anti-inflammatory Effects of Dietary Antioxidants
Current Medicinal Chemistry - Anti-Inflammatory & Anti-Allergy Agents Transplantation of Stem Cells as a Potential Therapeutic Strategy in Neurodegenerative Disorders
Current Stem Cell Research & Therapy Mechanisms of Action of Metformin in Type 2 Diabetes and Associated Complications: An Overview
Mini-Reviews in Medicinal Chemistry Functions of S100 Proteins
Current Molecular Medicine Editorial [The Multifactorial Nature of Alzheimers Disease and Related Therapeutic Strategies (Executive Editors: Maria do Carmo Carreiras and Jose Marco-Contelles)]
Current Pharmaceutical Design The Controversial Role of Adenosine A2A Receptor Antagonists as Neuro-protective Agents
Current Medicinal Chemistry - Central Nervous System Agents