Abstract
The pharmacological treatment of Parkinson´s disease (PD) is limited to dopamine agonists and anti-cholinergic drugs that do not stop the progress of disease. LDopa was introduced to the treatment in 1967; this drug is still the best and most commonly used drug since it generates a real improvement in patient quality of life, but the disadvantage of L-dopa is that this positive effect is followed by severe side effects such as dyskinesia. The search for a new drug in the treatment of PD is limited to compounds which decrease the side effects of the drugs used in the treatment of the disease, such as L-dopa-induced dyskinesia. One possible explanation for pharmaceutical companies not developing new drugs to stop disease development is because the mechanism which induces the loss of dopaminergic neurons containing neuromelanin of the nigrostriatal system is still unknown. The discovery of genes (alpha-synuclein, parkin, pink-1, DJ- 1, LRRK2, GBA1, etc.) associated with familial forms of PD resulted in an enormous input into basic research in order to understand the role of these proteins in the disease. It is generally accepted that the loss of dopaminergic neurons containing neuromelanin involves mitochondrial dysfunction, protein degradation dysfunction, the aggregation of alpha-synuclein to neurotoxic oligomers, oxidative neuroinflammation and endoplasmic reticulum stress, but the question of what induces these mechanisms remains unanswered. Aminochrome, the product of dopamine oxidation and the precursor of neuromelanin, is directly involved in five of the six mechanisms and may be a better PD preclinical model.
Keywords: Dopamine, drug metabolism, o-quinones, aminochrome, glutathione transferase M2-2, DT-diaphorase, Parkinson’s disease, neurodegeneration.
Current Medicinal Chemistry
Title:Aminochrome as New Preclinical Model to Find New Pharmacological Treatment that Stop the Development of Parkinson’s Disease
Volume: 23 Issue: 4
Author(s): Juan Segura-Aguilar, Patricia Muñoz and Irmgard Paris
Affiliation:
Keywords: Dopamine, drug metabolism, o-quinones, aminochrome, glutathione transferase M2-2, DT-diaphorase, Parkinson’s disease, neurodegeneration.
Abstract: The pharmacological treatment of Parkinson´s disease (PD) is limited to dopamine agonists and anti-cholinergic drugs that do not stop the progress of disease. LDopa was introduced to the treatment in 1967; this drug is still the best and most commonly used drug since it generates a real improvement in patient quality of life, but the disadvantage of L-dopa is that this positive effect is followed by severe side effects such as dyskinesia. The search for a new drug in the treatment of PD is limited to compounds which decrease the side effects of the drugs used in the treatment of the disease, such as L-dopa-induced dyskinesia. One possible explanation for pharmaceutical companies not developing new drugs to stop disease development is because the mechanism which induces the loss of dopaminergic neurons containing neuromelanin of the nigrostriatal system is still unknown. The discovery of genes (alpha-synuclein, parkin, pink-1, DJ- 1, LRRK2, GBA1, etc.) associated with familial forms of PD resulted in an enormous input into basic research in order to understand the role of these proteins in the disease. It is generally accepted that the loss of dopaminergic neurons containing neuromelanin involves mitochondrial dysfunction, protein degradation dysfunction, the aggregation of alpha-synuclein to neurotoxic oligomers, oxidative neuroinflammation and endoplasmic reticulum stress, but the question of what induces these mechanisms remains unanswered. Aminochrome, the product of dopamine oxidation and the precursor of neuromelanin, is directly involved in five of the six mechanisms and may be a better PD preclinical model.
Export Options
About this article
Cite this article as:
Segura-Aguilar Juan, Muñoz Patricia and Paris Irmgard, Aminochrome as New Preclinical Model to Find New Pharmacological Treatment that Stop the Development of Parkinson’s Disease, Current Medicinal Chemistry 2016; 23 (4) . https://dx.doi.org/10.2174/0929867323666151223094103
DOI https://dx.doi.org/10.2174/0929867323666151223094103 |
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
-
Riluzole, Neuroprotection and Amyotrophic Lateral Sclerosis
Current Medicinal Chemistry Essential Role of Gli Proteins in Glioblastoma Multiforme
Current Protein & Peptide Science Immunotherapy for Uveal Melanoma - Current Knowledge and Perspectives
Current Medicinal Chemistry Long Non-Coding RNA: An Emerging Paradigm of Pancreatic Cancer
Current Molecular Medicine Mitochondria: Prospective Targets for Neuroprotection in Parkinson's Disease
Current Pharmaceutical Design Serotonin Receptors of Type 6 (5-HT6): From Neuroscience to Clinical Pharmacology
Current Medicinal Chemistry The Novel Synthesized Pyridazinone Derivates had the Antiproliferative and Apoptotic Effects in SHSY5Y and HEP3B Cancer Cell Line
Letters in Organic Chemistry Targeting JAK/STAT Signaling Pathway in Inflammatory Diseases
Current Signal Transduction Therapy Immune System Modulation by Thyroid Axis Includes Direct Genomic and Nongenomic Actions of Thyroid Hormones on Immune Cells
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) Oncolytic Herpes Simplex Virus Type 1 and Host Immune Responses
Current Cancer Drug Targets ACE2-Ang-(1-7)-Mas Axis in Brain: A Potential Target for Prevention and Treatment of Ischemic Stroke
Current Neuropharmacology Recent Developments on Phenstatins as Potent Antimitotic Agents
Current Medicinal Chemistry Targeting Microtubules to Inhibit Angiogenesis and Disrupt Tumour Vasculature:Implications for Cancer Treatment
Current Cancer Drug Targets Sirtuins: Common Targets in Aging and in Neurodegeneration
Current Drug Targets Proteasome Inhibitors and Modulators of Angiogenesis in Multiple Myeloma
Current Medicinal Chemistry Cancer-Specific Ligands Identified from Screening of Peptide-Display Libraries
Current Pharmaceutical Design Endocrine Disruptors and Human Health
Mini-Reviews in Medicinal Chemistry Management of Glioblastoma Multiforme by Phytochemicals: Applications of Nanoparticle-Based Targeted Drug Delivery System
Current Drug Targets Antibody-Targeted Immunoliposomes for Cancer Treatment
Mini-Reviews in Medicinal Chemistry The Use of Cytokines and Chemokines in the Cancer Immunotherapy
Recent Patents on Anti-Cancer Drug Discovery