Etiologic Framework for the Study of Neurodegenerative Disorders as Well as Vascular and Metabolic Comorbidities on the Grounds of Shared Epidemiologic and Biologic Features
| Autor: | Alberto Rábano, María Ruiz-Tovar, Enrique Alcalde-Cabero, Jesús de Pedro-Cuesta, Pablo Martinez-Martin, Miguel Calero |
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| Přispěvatelé: | Centro de Investigación Biomedica en Red - CIBER, Instituto de Salud Carlos III, Unión Europea |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Aging Cognitive Neuroscience Population Multidisciplinary research overlaps Disease Bioinformatics templating underlying risk/progression 03 medical and health sciences 0302 clinical medicine Atrophy disease induction vs. transmission in amyloid Hypothesis and Theory etiology of conformational protein deposits Medicine Disease induction vs. transmission in amyloid education Gene Biomedicine multidisciplinary research overlaps education.field_of_study business.industry Transmission (medicine) Mechanism (biology) epidemiological patterns Type 2 Diabetes Mellitus Etiology of conformational protein deposits medicine.disease 030104 developmental biology Epidemiological patterns business 030217 neurology & neurosurgery Templating underlying risk/progression Neuroscience |
| Zdroj: | Repisalud Instituto de Salud Carlos III (ISCIII) Frontiers in Aging Neuroscience |
| Popis: | BACKGROUND: During the last two decades, protein aggregation at all organismal levels, from viruses to humans, has emerged from a neglected area of protein science to become a central issue in biology and biomedicine. This article constitutes a risk-based review aimed at supporting an etiologic scenario of selected, sporadic, protein-associated, i.e., conformational, neurodegenerative disorders (NDDs), and their vascular- and metabolic-associated ailments. METHODS: A rationale is adopted, to incorporate selected clinical data and results from animal-model research, complementing epidemiologic evidences reported in two prior articles. FINDINGS: Theory is formulated assuming an underlying conformational transmission mechanism, mediated either by horizontal transfer of mammalian genes coding for specific aggregation-prone proteins, or by xeno-templating between bacterial and host proteins. We build a few population-based and experimentally-testable hypotheses focusing on: (1) non-disposable surgical instruments for sporadic Creutzfeldt-Jakob disease (sCJD) and other rapid progressive neurodegenerative dementia (sRPNDd), multiple system atrophy (MSA), and motor neuron disease (MND); and (2) specific bacterial infections such as B. pertussis and E. coli for all forms, but particularly for late-life sporadic conformational, NDDs, type 2 diabetes mellitus (T2DM), and atherosclerosis where natural protein fibrils present in such organisms as a result of adaptation to the human host induce prion-like mechanisms. CONCLUSION: Implications for cohort alignment and experimental animal research are discussed and research lines proposed. Funding was received from the Consortium for Biomedical Research in Neurodegenerative Diseases (Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas/CIBERNED) as part of the 2014–2015 annual budget of the CIBERNED 509-group, and from the Carlos III Institute of Health (PI12/00045). Mr. Alcalde received support from the ISCIII Field Epidemiology Program during 2014 and 2015. The study was partially supported by a grant from the EU Joint Program—Neurodegenerative Disease Research (JPND—DEMTEST (Spanish Health Research Fund, FIS PI11/03021)). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. No author other than EAC received specific funding for this work. Sí |
| Databáze: | OpenAIRE |
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