Pharmacological Strategies to Improve Dendritic Spines in Alzheimer's Disease

Ettcheto, Miren; Busquets, Oriol; Cano, Amanda; Sanchez-Lopez, Elena; Manzine, Patricia R.; Espinosa-Jimenez, Triana; Verdaguer, Ester; Sureda, Francesc X.; Olloquequi, Jordi; Castro-Torres, Ruben D.; Auladell, Carme; Folch, Jaume; Casadesus, Gemma; Camins, Antoni


To deeply understand late onset Alzheimer's disease (LOAD), it may be necessary to change the concept that it is a disease exclusively driven by aging processes. The onset of LOAD could be associated with a previous peripheral stress at the level of the gut (changes in the gut microbiota), obesity (metabolic stress), and infections, among other systemic/environmental stressors. The onset of LOAD, then, may result from the generation of mild peripheral inflammatory processes involving cytokine production associated with peripheral stressors that in a second step enter the brain and spread out the process causing a neuroinflammatory brain disease. This hypothesis could explain the potential efficacy of Sodium Oligomannate (GV-971), a mixture of acidic linear oligosaccharides that have shown to remodel gut microbiota and slow down LOAD. However, regardless of the origin of the disease, the end goal of LOAD-related preventative or disease modifying therapies is to preserve dendritic spines and synaptic plasticity that underlay and support healthy cognition. Here we discuss how systemic/environmental stressors impact pathways associated with the regulation of spine morphogenesis and synaptic maintenance, including insulin receptor and the brain derived neurotrophic factor signaling. Spine structure remodeling is a plausible mechanism to maintain synapses and provide cognitive resilience in LOAD patients. Importantly, we also propose a combination of drugs targeting such stressors that may be able to modify the course of LOAD by acting on preventing dendritic spines and synapsis loss.

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Título según WOS: Pharmacological Strategies to Improve Dendritic Spines in Alzheimer's Disease
Volumen: 82
Editorial: IOS Press
Fecha de publicación: 2021
Página de inicio: S91
Página final: S107


Notas: ISI