Pharmacological Strategies to Improve Dendritic Spines in Alzheimer's Disease.

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.

• Authors: Miren Ettcheto, Oriol Busquets, Amanda Cano, Elena Sánchez-Lopez, Patricia R Manzine, Triana Espinosa-Jimenez, Ester Verdaguer, Francesc X Sureda, Jordi Olloquequi, Ruben D Castro-Torres, Carme Auladell, Jaume Folch, Gemma Casadesús, Antoni Camins
• Journal: Journal of Alzheimer's disease : JAD (J Alzheimers Dis) Vol. 82 Issue s1 Pg. S91-S107 ( 2021) ISSN: 1875-8908 [Electronic] Netherlands
• PMID: 33325386 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Amyloid beta-Peptides
• GV-971
• Oligosaccharides
• Mannose

Topics

• Alzheimer Disease (metabolism, psychology, therapy)
• Amyloid beta-Peptides (antagonists & inhibitors, metabolism)
• Animals
• Dendritic Spines (drug effects, pathology, physiology)
• Diet, Healthy (methods, psychology)
• Exercise (physiology, psychology)
• Gastrointestinal Microbiome (drug effects, physiology)
• Humans
• Mannose (administration & dosage, analogs & derivatives)
• Oligosaccharides (administration & dosage)
• Synapses (drug effects, pathology, physiology)