Abstract
Autophagy is the mechanism through which cells degrade oxidized membranes-organelles and mis/unfolded proteins, in this latter function cooperating with the ubiquitin-proteasome system (UP system). Although autophagy has been known for a long time, its involvement in the pathogenesis of neurodegenerative diseases has been investigated only recently. The most fascinating data are very recent and show an impressive connection between proteins that are mutated in different forms of familial Parkinsons Disease (PD) and the critical role that these proteins play in the physiology of the Autophagy (ATG) pathway. This evidence is supported by neuropathological data showing at the ultrastructural level, the occurrence of an altered ATG in the dopamine (DA) neurons of the Substantia Nigra of patients affected by PD. Accordingly, by using experimental models of PD the involvement of ATG is documented as well. In particular, administration of the DA neurotoxin methamphetamine produces damage to DA-containing cells which is exacerbated and results in neuronal cell death when the ATG pathway is inhibited, thus confirming ATG as a critical pathway for the survival of DA neurons. In the present manuscript, after describing the general molecular and cellular features of ATG, we give a short overview of the most relevant aspects concerning the involvement of ATG in the pathogenesis of PD. We further propose that the ATG and the UP systems might converge in the formation of a so-called “autophagoproteasome” which might represent an early ultrastructure witnessing the presence of an ongoing degeneration within DA cells.
Keywords: Parkinson's Disease, ATG, alpha-synuclein, dopamine, proteasome, autophagoproteasome, methamphetamine, lysosome
Current Topics in Medicinal Chemistry
Title: The Role of Autophagy on the Survival of Dopamine Neurons
Volume: 9 Issue: 10
Author(s): Ciro Isidoro, Francesca Biagioni, Filippo Sean Giorgi, Federica Fulceri, Antonio Paparelli and Francesco Fornai
Affiliation:
Keywords: Parkinson's Disease, ATG, alpha-synuclein, dopamine, proteasome, autophagoproteasome, methamphetamine, lysosome
Abstract: Autophagy is the mechanism through which cells degrade oxidized membranes-organelles and mis/unfolded proteins, in this latter function cooperating with the ubiquitin-proteasome system (UP system). Although autophagy has been known for a long time, its involvement in the pathogenesis of neurodegenerative diseases has been investigated only recently. The most fascinating data are very recent and show an impressive connection between proteins that are mutated in different forms of familial Parkinsons Disease (PD) and the critical role that these proteins play in the physiology of the Autophagy (ATG) pathway. This evidence is supported by neuropathological data showing at the ultrastructural level, the occurrence of an altered ATG in the dopamine (DA) neurons of the Substantia Nigra of patients affected by PD. Accordingly, by using experimental models of PD the involvement of ATG is documented as well. In particular, administration of the DA neurotoxin methamphetamine produces damage to DA-containing cells which is exacerbated and results in neuronal cell death when the ATG pathway is inhibited, thus confirming ATG as a critical pathway for the survival of DA neurons. In the present manuscript, after describing the general molecular and cellular features of ATG, we give a short overview of the most relevant aspects concerning the involvement of ATG in the pathogenesis of PD. We further propose that the ATG and the UP systems might converge in the formation of a so-called “autophagoproteasome” which might represent an early ultrastructure witnessing the presence of an ongoing degeneration within DA cells.
Export Options
About this article
Cite this article as:
Isidoro Ciro, Biagioni Francesca, Giorgi Sean Filippo, Fulceri Federica, Paparelli Antonio and Fornai Francesco, The Role of Autophagy on the Survival of Dopamine Neurons, Current Topics in Medicinal Chemistry 2009; 9 (10) . https://dx.doi.org/10.2174/156802609789378281
DOI https://dx.doi.org/10.2174/156802609789378281 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
Call for Papers in Thematic Issues
Chemistry Based on Natural Products for Therapeutic Purposes
The development of new pharmaceuticals for a wide range of medical conditions has long relied on the identification of promising natural products (NPs). There are over sixty percent of cancer, infectious illness, and CNS disease medications that include an NP pharmacophore, according to the Food and Drug Administration. Since NP ...read more
Current Trends in Drug Discovery Based on Artificial Intelligence and Computer-Aided Drug Design
Drug development discovery has faced several challenges over the years. In fact, the evolution of classical approaches to modern methods using computational methods, or Computer-Aided Drug Design (CADD), has shown promising and essential results in any drug discovery campaign. Among these methods, molecular docking is one of the most notable ...read more
Drug Discovery in the Age of Artificial Intelligence
In the age of artificial intelligence (AI), we have witnessed a significant boom in AI techniques for drug discovery. AI techniques are increasingly integrated and accelerating the drug discovery process. These developments have not only attracted the attention of academia and industry but also raised important questions regarding the selection ...read more
From Biodiversity to Chemical Diversity: Focus of Flavonoids
Flavonoids are the largest group of polyphenols, plant secondary metabolites arising from the essential aromatic amino acid phenylalanine (or more rarely from tyrosine) via the phenylpropanoid pathway. The flavan nucleus is the basic 15-carbon skeleton of flavonoids (C6-C3-C6), which consists of two phenyl rings (A and B) and a heterocyclic ...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
-
PHB in Cardiovascular and Other Diseases: Present Knowledge and Implications
Current Drug Targets The Genetic Background of Cholesterol Gallstone Formation: An Inventory of Human Lithogenic Genes
Current Drug Targets - Immune, Endocrine & Metabolic Disorders Understanding Respiratory Syncytial Virus Infection to Improve Treatment and Immunity
Current Molecular Medicine Relevance of Postprandial Lipemia in Metabolic Syndrome
Current Vascular Pharmacology Alzheimer’s Disease And Type 2 Diabetes: Exploring The Association To Obesity And Tyrosine Hydroxylase
CNS & Neurological Disorders - Drug Targets Potential Targets for Intervention in Radiation-Induced Heart Disease
Current Drug Targets Human Amniotic Fluid Stem Cells as an Attractive Tool for Clinical Applications
Current Stem Cell Research & Therapy Safety Issues of Vitamin D Supplementation
Anti-Cancer Agents in Medicinal Chemistry Adrenomedullin as a Potential Therapeutic Agent for Inflammatory Bowel Disease
Current Protein & Peptide Science Heart Failure in South America
Current Cardiology Reviews Antiplatelet and Anticoagulation Therapy in Structural Heart Disease Interventions Beyond TAVI
Current Pharmaceutical Design Comparison between Atorvastatin and Rosuvastatin on Secondary Percutaneous Coronary Intervention Rate and the Risk Factors in Patients with Coronary Heart Disease
Current Drug Metabolism Leukocyte P2 Receptors: A Novel Target for Anti-inflammatory and Antitumor Therapy
Current Drug Targets - Cardiovascular & Hematological Disorders Application of Nanomedicine in Cardiovascular Diseases and Stroke
Current Pharmaceutical Design Pre-CKD- Do we Need Another Hero?
Current Vascular Pharmacology Myricetin Induces Apoptosis in HepG2 Cells Through Akt/p70S6K/Bad Signaling and Mitochondrial Apoptotic Pathway
Anti-Cancer Agents in Medicinal Chemistry Evolving Strategies in Manipulating VEGF/VEGFR Signaling for the Promotion of Angiogenesis in Ischemic Muscle
Current Pharmaceutical Design The Metabolic Syndrome and HIV Infection
Current Pharmaceutical Design Platelets and Vascular Risk: An Option for Treatment
Current Pharmaceutical Design Mutations of Nuclear and Mitochondrial Genomes as Potential Targets for the Treatment of Metabolic Syndrome
Current Pharmaceutical Design