Title | Pharmacological Strategies to Improve Dendritic Spines in Alzheimer's Disease. |
Publication Type | Journal Article |
Year of Publication | 2021 |
Authors | Ettcheto, M, Busquets, O, Cano, A, Sánchez-López, E, Manzine, PR, Espinosa-Jimenez, T, Verdaguer, E, Sureda, FX, Olloquequi, J, Castro-Torres, RD, Auladell, C, Folch, J, Casadesus, G, Camins, A |
Journal | J Alzheimers Dis |
Volume | 82 |
Issue | s1 |
Pagination | S91-S107 |
Date Published | 2021 |
ISSN | 1875-8908 |
Keywords | Alzheimer Disease, Amyloid beta-Peptides, Animals, Dendritic Spines, Diet, Healthy, Exercise, Gastrointestinal Microbiome, Humans, Mannose, Oligosaccharides, Synapses |
Abstract | 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 slowdown 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. |
DOI | 10.3233/JAD-201106 |
Alternate Journal | J Alzheimers Dis |
PubMed ID | 33325386 |