Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/141943
Title: A metabolic perspective of late onset Alzheimer's disease
Author: Ettcheto Arriola, Miren
Cano Fernández, Amanda
Busquets Figueras, Oriol
Manzine, Patricia
Sánchez-López, E. (Elena)
Castro Torres, Ruben Dario
Beas Zárate, Carlos
Verdaguer Cardona, Ester
García López, María Luisa
Olloquequi González, Jordi
Auladell i Costa, M. Carme
Folch López, Jaume
Camins Espuny, Antoni
Keywords: Malaltia d'Alzheimer
Diabetis
Metabolisme
Alzheimer's disease
Diabetes
Metabolism
Issue Date: 13-Apr-2019
Publisher: Elsevier B.V.
Abstract: After decades of research, the molecular neuropathology of Alzheimer's disease (AD) is still one of the hot topics in biomedical sciences. Some studies suggest that soluble amyloid β (Aβ) oligomers act as causative agents in the development of AD and could be initiators of its complex neurodegenerative cascade. On the other hand, there is also evidence pointing to Aβ oligomers as mere aggravators, with an arguable role in the origin of the disease. In this line of research, the relative contribution of soluble Aβ oligomers to neuronal damage associated with metabolic disorders such as Type 2 Diabetes Mellitus (T2DM) and obesity is being actively investigated. Some authors have proposed the endoplasmic reticulum (ER) stress and the induction of the unfolded protein response (UPR) as important mechanisms leading to an increase in Aβ production and the activation of neuroinflammatory processes. Following this line of thought, these mechanisms could also cause cognitive impairment. The present review summarizes the current understanding on the neuropathological role of Aβ associated with metabolic alterations induced by an obesogenic high fat diet (HFD) intake. It is believed that the combination of these two elements has a synergic effect, leading to the impairement of ER and mitochondrial functions, glial reactivity status alteration and inhibition of insulin receptor (IR) signalling. All these metabolic alterations would favour neuronal malfunction and, eventually, neuronal death by apoptosis, hence causing cognitive impairment and laying the foundations for late-onset AD (LOAD). Moreover, since drugs enhancing the activation of cerebral insulin pathway can constitute a suitable strategy for the prevention of AD, we also discuss the scope of therapeutic approaches such as intranasal administration of insulin in clinical trials with AD patients.
Note: Versió postprint del document publicat a: https://doi.org/10.1016/j.phrs.2019.104255
It is part of: Pharmacological Research, 2019
URI: http://hdl.handle.net/2445/141943
Related resource: https://doi.org/10.1016/j.phrs.2019.104255
ISSN: 1043-6618
Appears in Collections:Articles publicats en revistes (Farmacologia, Toxicologia i Química Terapèutica)
Articles publicats en revistes (Biologia Cel·lular, Fisiologia i Immunologia)

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