Etiologic Framework for the Study of Neurodegenerative Disorders as Well as Vascular and Metabolic Comorbidities on the Grounds of Shared Epidemiologic and Biologic Features.

Jesús De Pedro-Cuesta,Enrique Alcalde-Cabero,Alberto Rábano,Miguel Calero,María Ruiz-Tovar,Pablo Martínez-Martín

doi:10.3389/fnagi.2016.00138

Abstract

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.

Highlights

We build a few population-based and experimentally-testable hypotheses focusing on: (1) non-disposable surgical instruments for sporadic Creutzfeldt-Jakob disease and other rapid progressive neurodegenerative dementia, 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 for latelife sporadic conformational, neurodegenerative disorders (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
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 (Villar-Piqué and Ventura, 2012) The expanding knowledge in the field has benefited our understanding of neurodegenerative disorders (NDDs)
We used a modified definition of the driver concept proposed by Sutherland to identify risk factors of specific proteins affecting different NDDs (Sutherland et al, 2011) and, having in mind the common amyloid nature of the pathogenic proteins involved, we identified selected traits of the epidemiology of sporadic, protein-associated, i.e., conformational, NDDs useful for interpreting epidemiologic findings and relationships of the entities listed in Table 1 (Gunnarsson et al, 1996; Marmorstein et al, 2002; Peng et al, 2005; Irwin et al, 2013; Prusiner et al, 2015; de Pedro-Cuesta et al, 2016)

Summary

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

Conclusion

INTRODUCTION