Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
6286489 | Progress in Neurobiology | 2014 | 22 Pages |
Abstract
Alzheimer's disease (AD) is the most common cause of dementia, affecting more than 36 million people worldwide. AD is characterized by a progressive loss of cognitive functions. For years, it has been thought that age is the main risk factor for AD. Recent studies suggest that life style factors, including nutritional behaviors, play a critical role in the onset of dementia. Evidence about the relationship between nutritional behavior and AD includes the role of conditions such as obesity, hypertension, dyslipidemia and elevated glucose levels. The coexistence of some of these cardio-metabolic risk factors is generally known as metabolic syndrome (MS). Some clinical studies support the role of MS in the onset of AD. However, the cross-talk between the molecular signaling implicated in these disorders is unknown. In the present review, we focus on the molecular correlates that support the relationship between MS and the onset of AD. We also discuss relevant issues such as the role of leptin, insulin and renin-angiotensin signaling in the brain and the possible role of Wnt signaling in both MS and AD. We discuss the evidence supporting the use of ob/ob mice, high-fructose diets, aortic coarctation-induced hypertension and Octodon degus, which spontaneously develops β-amyloid deposits and metabolic derangements, as suitable animal models to address the relationships between MS and AD. Finally, we examine emergent data supporting the role of Wnt signaling in the modulation of AD and MS, implicating this pathway as a therapeutic target in both conditions.
Keywords
PCPAβIL-18WntACEDVLIRS-1NFTsPLCBMP-4RASTACTCFPPARγGSK-3βIL-1βpKaAPPAMPKHDLSFRP1DKK1LRPFZDfrizzledJGAPI3KT2DMASCVDLRBABCA7SORL1AMP-activated protein kinaseC/EBPαCCAAT/enhancer binding protein αERK1/2high-density lipoproteinextracellular-signal-regulated kinasesROSSTATangiotensin converting enzymeinsulin-degrading enzymeAngiotensin Iangiotensin-IIAngiotensin IIapolipoprotein JIncretinsinsulininsulin receptor substrate-1Interleukin-18Interleukin-1βIDEdisheveledAlzheimer's diseaseAtherosclerotic cardiovascular diseaselong-term potentiationLTPtumor necrosis factor-αJuxtaglomerular apparatusCNSAng IIType 2 diabetes mellitusdiacylglycerolDAGBBBBlood–brain barrierAgeMetabolic syndromeCerebral Spinal FluidRenin–angiotensin systemcentral nervous systembody mass indexBMIDickkopf 1lymphoid enhancer-binding factorTNF-αphosphatidylinositide 3-kinasesphospholipase CBlood pressureLefLeptinLow-density lipoproteinLDLCSFAdvanced glycation end productsAng IApoJneurofibrillary tanglesLipoprotein receptor-related proteinbone morphogenetic protein 4Secreted frizzled-related protein 1amyloid precursor proteinprotein kinase Aamyloid-β peptideJAKGlycogen synthase kinase-3βReactive oxygen speciesinsulin receptorLeptin receptorAngiotensin II receptors
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Authors
Juvenal A. RÃos, Pedro Cisternas, Marco Arrese, Salesa Barja, Nibaldo C. Inestrosa,