期刊
FRONTIERS IN PHYSIOLOGY
卷 5, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fphys.2014.00522
关键词
age-related disease; mitochondrial dysregulation; metabolic alteration; the Inverse Warburg effect; inverse cancer comorbidity
类别
资金
- Swiss Fonds National de la Recherche [3100A3_140957, 31003A-130821/1]
- National Centre of Competence in Research Synapsy [310030B-148169/1]
- Biaggi Foundation
- Panacee Foundation
- Swiss National Science Foundation (SNF) [310030B_148169, 31003A_130821] Funding Source: Swiss National Science Foundation (SNF)
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.
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