Reporter: Aviva Lev-Ari, PhD, RN
The inverse association of cancer and Alzheimer’s: a bioenergetic mechanism.
Source
Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA. ldemetr@oeb.harvard.edu
Abstract
The sporadic forms of cancer and Alzheimer’s disease (AD) are both age-related metabolic disorders. However, the molecular mechanisms underlying the two diseases are distinct: cancer is described by essentially limitless replicative potential, whereas neuronal death is a key feature of AD. Studies of the origin of both diseases indicate that their sporadic forms are the result of metabolic dysregulation, and a compensatory increase in energy transduction that is inversely related. In cancer, the compensatory metabolic effect is the upregulation of glycolysis-the Warburg effect; in AD, a bioenergetic model based on the interaction between astrocytes and neurons indicates that the compensatory metabolic alteration is the upregulation of oxidative phosphorylation-an inverse Warburg effect. These two modes of metabolic alteration could contribute to an inverse relation between the incidence of the two diseases. We invoke this bioenergetic mechanism to furnish a molecular basis for an epidemiological observation, namely the incidence of sporadic forms of cancer and AD is inversely related. We furthermore exploit the molecular mechanisms underlying the diseases to propose common therapeutic strategies for cancer and AD based on metabolic intervention.
- PMID: 23427097
- PMCID: PMC3627084
- [Available on 2014/5/6]
- http://www.ncbi.nlm.nih.gov/pubmed/23427097?goback=%2Egde_2171620_member_248103990
2012pharmaceutical
Aashir Awan, Phd
Alan F. Kaul, PharmD., MS, MBA, FCCP
alexcrystal6
anamikasarkar
apreconasia
aviralvatsa
David Orchard-Webb, PhD
danutdaagmailcom
Demet Sag, Ph.D., CRA, GCP
Daniel Menzin
Dror Nir
evelinacohn
Gail S Thornton
Irina Robu
jdpmd
jshertok
kellyperlman
Ed Kislauskis
larryhbern
marzankhan
megbaker58
ofermar2020
pkandala
Rosalind Codrington, PhD
ritusaxena
Rick Mandahl
sjwilliamspa
stuartlpbi
Dr. Sudipta Saha
tildabarliya
zraviv06
zs22
J Bioenerg Biomembr. 2007 Jun;39(3):267-74.
The Warburg effect and its cancer therapeutic implications.
Chen Z, Lu W, Garcia-Prieto C, Huang P.
Source
Department of Molecular Pathology, The University of Texas MD Anderson Cancer Center, 7435 Fannin Street, Houston, TX 77030, USA.
Abstract
Increased aerobic glycolysis in cancer, a phenomenon known as the Warburg effect, has been observed in various tumor cells and represents a major biochemical alteration associated with malignant transformation. Although the exact molecular mechanisms underlying this metabolic change remain to be elucidated, the profound biochemical alteration in cancer cell energy metabolism provides exciting opportunities for the development of therapeutic strategies to preferentially kill cancer cells by targeting the glycolytic pathway. Several small molecules capable of inhibiting glycolysis in experimental systems have been shown to have promising anticancer activity in vitro and in vivo. This review article provides a brief summary of our current understanding of the Warburg effect, the underlying mechanisms, and its influence on the development of therapeutic strategies for cancer treatment.
PMID: 17551814 [PubMed – indexed for MEDLINE]
Antioxid Redox Signal. 2012 Jun 15;16(12):1476-91. doi: 10.1089/ars.2011.4259. Epub 2011 Oct 26.
Strategic role for mitochondria in Alzheimer’s disease and cancer.
Hedskog L, Zhang S, Ankarcrona M.
Source
Department of Neurobiology, Care Sciences and Society (NVS), KI-Alzheimer Disease Research Center, Karolinska Institutet, Stockholm, Sweden.
Abstract
SIGNIFICANCE:
Detailed knowledge about cell death and cell survival mechanisms and how these pathways are impaired in neurodegenerative disorders and cancer forms the basis for future drug development for these diseases that affect millions of people around the world. RECENT ADVANCES: In neurodegenerative disorders such as Alzheimer’s disease (AD), cell death pathways are inappropriately activated, resulting in neuronal cell death. In contrast, cancer cells develop resistance to apoptosis by regulating anti-apoptotic proteins signaling via mitochondria. Mounting evidence shows that mitochondrial function is central in both cancer and AD. Cancer cells typically shut down oxidative phosphorylation (OXPHOS) in mitochondria and switch to glycolysis for ATP production, making them resistant to hypoxia. In AD, for example, amyloid-β peptide (Aβ) and reactive oxygen species impair mitochondrial function. Neurons therefore also switch to glycolysis to maintain ATP production and to produce molecules involved in antioxidant metabolism in an attempt to survive.
CRITICAL ISSUES:
One critical difference between cancer cells and neurons is that cancer cells can survive without OXPHOS, while neurons are dependent on OXPHOS for long-term survival.
FUTURE DIRECTIONS:
This review will focus on these abnormalities of mitochondrial function shared in AD and cancer and discuss the potential mechanisms underlying links that may be key steps in the development of therapeutic strategies.
LinksbetweencopperandcholesterolinAlzheimer’sdisease
YaHuiHung1,2*, AshleyI.Bush1,3 and SharonLaFontaine4,5
1 OxidationBiologyLaboratory,FloreyInstituteofNeuroscienceandMentalHealth,Parkville,VIC,Australia
2 CentreforNeuroscienceResearch,TheUniversityofMelbourne,Parkville,VIC,Australia
3 DepartmentofPathology,TheUniversityofMelbourne,Parkville,VIC,Australia
4 StrategicResearchCentreforMolecularandMedicalResearch,DeakinUniversity,Burwood,VIC,Australia
5 CentreforCellularandMolecularBiology,SchoolofLifeandEnvironmentalSciences,DeakinUniversity,Burwood,VIC,Australia
Editedby:
AlessandroPrinetti,Universityof
Milano,Italy
Reviewedby:
LuisM.S.Loura,Universityof
Coimbra,Portugal
RobertoCappai,TheUniversityof
Melbourne,Australia
*Correspondence:
YaHuiHung,OxidationBiology
Laboratory,FloreyInstituteof
NeuroscienceandMentalHealth,
KennethMyerBuilding,AtGenetics
LaneonRoyalParade,The
UniversityofMelbourne,VIC3010,
Australia.
e-mail: yahui.hung@florey.edu.au
AlteredcopperhomeostasisandhypercholesterolemiahavebeenidentifiedindependentlyasriskfactorsforAlzheimer’sdisease(AD).Abnormalcopperandcholesterolmetabolismareimplicatedinthegenesisofamyloidplaquesandneurofibrillarytangles(NFT),whicharetwokeypathologicalsignaturesofAD.Amyloidogenicprocessingofasub-populationofamyloidprecursorprotein(APP)thatproducesAβoccursincholesterol-richlipidraftsincopperdeficientADbrains.Co-localizationofAβandaparadoxicalhighconcentrationofcopperinlipidraftsfosterstheformationofneurotoxicAβ:coppercomplexes.ThesecomplexescancatalyticallyoxidizecholesteroltogenerateH2O2,oxysterolsandotherlipidperoxidationproductsthataccumulateinbrainsofADcasesandtransgenicmousemodels.Tau,thecoreproteincomponentofNFTs,issensitivetointeractionswithcopperandcholesterol,whichtriggeracascadeofhyperphosphorylationandaggregationprecedingthegenerationofNFTs.Herewepresentanoverviewofcopperandcholesterolmetabolisminthebrain,andhowtheirintegratedfailurecontributestodevelopmentofAD.
Keywords:copper,cholesterol,Alzheimer’sdisease,ApoE,amyloidprecursorprotein,Aβ, tau,lipidrafts
Last comment need editing.
PLEASE MAKE YOUR POINT, I do not follow your argument !!
Then you haven’t read the items. The study posted doesn’t hold up based on any knowledge of mitochondrial energetics, and it completely ignores the importance of ubiquitination. I’m extremely busy now, so I had not intended presenting this – non-argument – at this or any other time.
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