Alzheimer's disease: the amyloid hypothesis and the Inverse Warburg effect.
Details
State: Public
Version: Final published version
Serval ID
serval:BIB_62F93479F3D1
Type
Article: article from journal or magazin.
Publication sub-type
Review (review): journal as complete as possible of one specific subject, written based on exhaustive analyses from published work.
Collection
Publications
Institution
Title
Alzheimer's disease: the amyloid hypothesis and the Inverse Warburg effect.
Journal
Frontiers in Physiology
ISSN
1664-042X (Electronic)
ISSN-L
1664-042X
Publication state
Published
Issued date
01/2015
Peer-reviewed
Oui
Volume
5
Pages
522
Language
english
Notes
Publication types: Journal Article Publication Status: epublish
Abstract
Epidemiological and biochemical studies show that the sporadic forms of Alzheimer's disease (AD) are characterized by the following hallmarks: (a) An exponential increase with age; (b) Selective neuronal vulnerability; (c) Inverse cancer comorbidity. The present article appeals to these hallmarks to evaluate and contrast two competing models of AD: the amyloid hypothesis (a neuron-centric mechanism) and the Inverse Warburg hypothesis (a neuron-astrocytic mechanism). We show that these three hallmarks of AD conflict with the amyloid hypothesis, but are consistent with the Inverse Warburg hypothesis, a bioenergetic model which postulates that AD is the result of a cascade of three events-mitochondrial dysregulation, metabolic reprogramming (the Inverse Warburg effect), and natural selection. We also provide an explanation for the failures of the clinical trials based on amyloid immunization, and we propose a new class of therapeutic strategies consistent with the neuroenergetic selection model.
Pubmed
Web of science
Open Access
Yes
Create date
05/02/2015 14:28
Last modification date
20/08/2019 15:19