PMID- 23086530
OWN - NLM
STAT- MEDLINE
DCOM- 20130524
LR  - 20220408
IS  - 1573-6768 (Electronic)
IS  - 1389-5729 (Linking)
VI  - 13
IP  - 6
DP  - 2012 Dec
TI  - An inverse-Warburg effect and the origin of Alzheimer's disease.
PG  - 583-94
LID - 10.1007/s10522-012-9403-6 [doi]
AB  - Glycolysis and oxidative phosphorylation (OxPhos) are the two major mechanisms 
      involved in brain energetics. In this article we propose that the sporadic forms 
      of Alzheimer's disease (AD) are driven by age-related damage to macromolecules 
      and organelles which results in the following series of dynamic processes. (1) 
      Metabolic alteration: Upregulation of OxPhos activity by dysfunctional neurons. 
      (2) Natural selection: Competition for the limited energy substrates between 
      neurons with normal OxPhos activity [Type (1)] and dysfunctional neurons with 
      increased OxPhos [Type (2)]. (3) Propagation, due to the fact that Type (1) 
      neurons are outcompeted for limited substrate by Type (2) neurons which, because 
      of increased ROS production, eventually become dysfunctional and die. Otto 
      Warburg, in his studies of the origin of cancer, discovered that most cancer 
      cells are characterized by an increase in glycolytic activity-a property which 
      confers a selective advantage in oncologic environments. Accordingly, we propose 
      the term "inverse-Warburg effect" to describe increased OxPhos activity--a 
      property which we propose confers a selective advantage in neuronal environments, 
      and which we hypothesize to underlie the shift from normal to pathological aging 
      and subsequent AD.
FAU - Demetrius, Lloyd A
AU  - Demetrius LA
AD  - Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, 
      MA 02138, USA. ldemetr@oeb.harvard.edu
FAU - Simon, David K
AU  - Simon DK
LA  - eng
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20121020
PL  - Netherlands
TA  - Biogerontology
JT  - Biogerontology
JID - 100930043
RN  - 0 (Reactive Oxygen Species)
SB  - IM
MH  - Aging/*metabolism
MH  - Alzheimer Disease/*metabolism
MH  - Astrocytes/metabolism
MH  - Brain/*metabolism
MH  - *Energy Metabolism
MH  - *Glycolysis
MH  - Humans
MH  - Mitochondria/metabolism
MH  - Models, Theoretical
MH  - Neurons/metabolism
MH  - *Oxidative Phosphorylation
MH  - Oxidative Stress
MH  - Reactive Oxygen Species/metabolism
EDAT- 2012/10/23 06:00
MHDA- 2013/05/28 06:00
CRDT- 2012/10/23 06:00
PHST- 2012/05/02 00:00 [received]
PHST- 2012/09/28 00:00 [accepted]
PHST- 2012/10/23 06:00 [entrez]
PHST- 2012/10/23 06:00 [pubmed]
PHST- 2013/05/28 06:00 [medline]
AID - 10.1007/s10522-012-9403-6 [doi]
PST - ppublish
SO  - Biogerontology. 2012 Dec;13(6):583-94. doi: 10.1007/s10522-012-9403-6. Epub 2012 
      Oct 20.