Abstract
Conformational Protein Diseases (CPDs) comprise over forty clinically and pathologically diverse disorders in which specific altered proteins accumulate in cells or tissues of the body. The most studied are Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, prion diseases, inclusion body myopathy, and the systemic amyloidoses. They are characterised by three dimensional conformational alterations, which are often rich in β- structure. Proteins in this non-native conformation are highly stable, resistant to degradation, and have an enhanced tendency to aggregate with like protein molecules. The misfolded proteins can impart their anomalous properties to soluble, monomeric proteins with the same amino acid sequence by a process that has been likened to seeded crystallization. However, these potentially pathogenic proteins also have important physiological actions, which have not completely characterized. This opens up the question of what process transforms physiological actions into pathological actions and most intriguing, is why potentially dangerous proteins have been maintained during evolution and are present from yeasts to humans. In the present paper, we introduce the concept of mis–exaptation and of mis–tinkering since they may help in clarifying some of the double edged sword aspects of these proteins. Against this background an original interpretative paradigm for CPDs will be given in the frame of the previously proposed Red Queen Theory of Aging.
Keywords: Exaptation, tinkering, neurodegenerative diseases, prions, protein conformation, protein aggregation, aging
Current Protein & Peptide Science
Title:A New Interpretative Paradigm for Conformational Protein Diseases
Volume: 14 Issue: 2
Author(s): Luigi Francesco Agnati, Diego Guidolin, Amina S. Woods, Francisco Ciruela, Chiara Carone, Annamaria Vallelunga, Dasiel Oscar Borroto Escuela, Susanna Genedani and Kjell Fuxe
Affiliation:
Keywords: Exaptation, tinkering, neurodegenerative diseases, prions, protein conformation, protein aggregation, aging
Abstract: Conformational Protein Diseases (CPDs) comprise over forty clinically and pathologically diverse disorders in which specific altered proteins accumulate in cells or tissues of the body. The most studied are Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, prion diseases, inclusion body myopathy, and the systemic amyloidoses. They are characterised by three dimensional conformational alterations, which are often rich in β- structure. Proteins in this non-native conformation are highly stable, resistant to degradation, and have an enhanced tendency to aggregate with like protein molecules. The misfolded proteins can impart their anomalous properties to soluble, monomeric proteins with the same amino acid sequence by a process that has been likened to seeded crystallization. However, these potentially pathogenic proteins also have important physiological actions, which have not completely characterized. This opens up the question of what process transforms physiological actions into pathological actions and most intriguing, is why potentially dangerous proteins have been maintained during evolution and are present from yeasts to humans. In the present paper, we introduce the concept of mis–exaptation and of mis–tinkering since they may help in clarifying some of the double edged sword aspects of these proteins. Against this background an original interpretative paradigm for CPDs will be given in the frame of the previously proposed Red Queen Theory of Aging.
Export Options
About this article
Cite this article as:
Francesco Agnati Luigi, Guidolin Diego, S. Woods Amina, Ciruela Francisco, Carone Chiara, Vallelunga Annamaria, Oscar Borroto Escuela Dasiel, Genedani Susanna and Fuxe Kjell, A New Interpretative Paradigm for Conformational Protein Diseases, Current Protein & Peptide Science 2013; 14 (2) . https://dx.doi.org/10.2174/1389203711314020006
DOI https://dx.doi.org/10.2174/1389203711314020006 |
Print ISSN 1389-2037 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5550 |
Call for Papers in Thematic Issues
Advancements in Proteomic and Peptidomic Approaches in Cancer Immunotherapy: Unveiling the Immune Microenvironment
The scope of this thematic issue centers on the integration of proteomic and peptidomic technologies into the field of cancer immunotherapy, with a particular emphasis on exploring the tumor immune microenvironment. This issue aims to gather contributions that illustrate the application of these advanced methodologies in unveiling the complex interplay ...read more
Artificial Intelligence for Protein Research
Protein research, essential for understanding biological processes and creating therapeutics, faces challenges due to the intricate nature of protein structures and functions. Traditional methods are limited in exploring the vast protein sequence space efficiently. Artificial intelligence (AI) and machine learning (ML) offer promising solutions by improving predictions and speeding up ...read more
Nutrition and Metabolism in Musculoskeletal Diseases
The musculoskeletal system consists mainly of cartilage, bone, muscles, tendons, connective tissue and ligaments. Balanced metabolism is of vital importance for the homeostasis of the musculoskeletal system. A series of musculoskeletal diseases (for example, sarcopenia, osteoporosis) are resulted from the dysregulated metabolism of the musculoskeletal system. Furthermore, metabolic diseases (such ...read more
Protein Folding, Aggregation and Liquid-Liquid Phase Separation
Protein folding, misfolding and aggregation remain one of the main problems of interdisciplinary science not only because many questions are still open, but also because they are important from the point of view of practical application. Protein aggregation and formation of fibrillar structures, for example, is a hallmark of a ...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
Related Articles
-
Neurodegenerative Diseases and Flavonoids: Special Reference to Kaempferol
CNS & Neurological Disorders - Drug Targets Copper Status Abnormalities and How to Measure Them in Neurodegenerative Disorders
Recent Patents on CNS Drug Discovery (Discontinued) Antioxidants in the Practice of Medicine; What Should the Clinician Know?
Cardiovascular & Hematological Disorders-Drug Targets Small Heat Shock Proteins and Protein-Misfolding Diseases
Current Pharmaceutical Biotechnology XBP-1 and the UPRosome: Mastering Secretory Cell Function
Current Immunology Reviews (Discontinued) The Roles of Mesenchymal Stem Cells in Tissue Repair and Disease Modification
Current Stem Cell Research & Therapy Blood-Brain Barrier P-Glycoprotein Function in Neurodegenerative Disease
Current Pharmaceutical Design Involvement of the Mitochondrial Benzodiazepine Receptor in Traumatic Brain Injury: Therapeutic Implications
CNS & Neurological Disorders - Drug Targets Glutamate Binding-Site Ligands of NMDA Receptors
Current Medicinal Chemistry Neurodegeneration and Neuroprotection in Multiple Sclerosis
Current Pharmaceutical Design MicroRNAs: Macro Challenges on Understanding Human Biological Functions and Neurological Diseases
Current Molecular Medicine Conformational Diseases: Structural Studies of Aggregation of Polyglutamine Proteins
Current Computer-Aided Drug Design Memory Enhancing Effect of Black Pepper in the AlCl3 Induced Neurotoxicity Mouse Model is Mediated Through Its Active Component Chavicine
Current Pharmaceutical Biotechnology Protective Effects of the Caffeine Against Neurodegenerative Diseases
Current Medicinal Chemistry Novel Approaches for Potential Therapy of Cystic Fibrosis
Current Drug Targets Partnerships Between Philanthropy, Government and Investors are Needed to Advance Drug Discovery for Neurodegenerative Diseases
Current Alzheimer Research Intracellular Calcium Homeostasis and Kidney Disease
Current Medicinal Chemistry AAV as a Gene Transfer Vector for the Treatment of Neurological Disorders: Novel Treatment Thoughts for ALS
Current Gene Therapy Effects of Coenzyme Q and Creatine Supplementation on Brain Energy Metabolism in Rats Exposed to Chronic Cerebral Hypoperfusion
Current Alzheimer Research Can Trehalose Prevent Neurodegeneration? Insights from Experimental Studies
Current Drug Targets