Is Alzheimer's Disease related to Metabolic Syndrome? A Wnt Signaling Conundrum

Is Alzheimer’s Disease related to Metabolic Syndrome?
A Wnt Signaling Conundrum

Juvenal A. Ríos, Pedro Cisternas, Marco Arrese, Salesa
Barja and Nibaldo C. Inestrosa

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/obmice, 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.

New Review with drawings: Alzheimer’s disease: relevant molecular and physiopathological events affecting amyloid-β brain balance and the putative role of PPARs.

Alzheimer’s disease: relevant molecular and physiopathological events affecting amyloid-β brain balance and the putative role of PPARs.

Juan M. Zolezzi, Sussy Bastías-Candia, Manuel J. Santos and Nibaldo C. Inestrosa

New Review !! "Signaling pathway cross talk in Alzheimer’s disease"

Signaling pathway cross talk in Alzheimer’s disease

Juan A Godoy¹, Juvenal A Rios¹, Juan M Zolezzi², Nady Braidy³ and Nibaldo C Inestrosa^13*

Abstract

Numerous studies suggest energy failure and accumulative intracellular waste play a causal role in the pathogenesis of several neurodegenerative disorders and Alzheimer’s disease (AD) in particular. AD is characterized by extracellular amyloid deposits, intracellular neurofibrillary tangles, cholinergic deficits, synaptic loss, inflammation and extensive oxidative stress. These pathobiological changes are accompanied by significant behavioral, motor, and cognitive impairment leading to accelerated mortality. Currently, the potential role of several metabolic pathways associated with AD, including Wnt signaling, 5' adenosine monophosphate-activated protein kinase (AMPK), mammalian target of rapamycin (mTOR), Sirtuin 1 (Sirt1, silent mating-type information regulator 2 homolog 1), and peroxisome proliferator-activated receptor gamma co-activator 1-α (PGC-1α) have widened, with recent discoveries that they are able to modulate several pathological events in AD. These include reduction of amyloid-β aggregation and inflammation, regulation of mitochondrial dynamics, and increased availability of neuronal energy. This review aims to highlight the involvement of these new set of signaling pathways, which we have collectively termed “anti-ageing pathways”, for their potentiality in multi-target therapies against AD where cellular metabolic processes are severely impaired.