The Potential Role of Integrin Signaling in Memory and Cognitive Impairment

Abstract

Dementia currently has no cure and, due to the increased prevalence and associated economic and personal burden of this condition, current research efforts for the development of potential therapies have intensified. Recently, targeting integrins as a strategy to ameliorate dementia and other forms of cognitive impairment has begun to gain traction. Integrins are major bidirectional signaling receptors in mammalian cells, mediating various physiological processes such as cell–cell interaction and cell adhesion, and are also known to bind to the extracellular matrix. In particular, integrins play a critical role in the synaptic transmission of signals, hence their potential contribution to memory formation and significance in cognitive impairment. In this review, we describe the physiological roles that integrins play in the blood–brain barrier (BBB) and in the formation of memories. We also provide a clear overview of how integrins are implicated in BBB disruption following cerebral pathology. Given that vascular contributions to cognitive impairment and dementia and Alzheimer’s’ disease are prominent forms of dementia that involve BBB disruption, as well as chronic inflammation, we present current approaches shown to improve dementia-like conditions with integrins as a central focus. We conclude that integrins are vital in memory formation and that their disruption could lead to various forms of cognitive impairment. While further research to understand the relationships between integrins and memory is needed, we propose that the translational relevance of research efforts in this area could be improved through the use of appropriately aged, comorbid, male and female animals.

The effect of human PBMCs immobilization on their Аβ42 aggregates-dependent proinflammatory state on a cellular model of Alzheimer’s disease

“…A decrease in the ratio of Aβ42/40 against the background of an increase in the level of insoluble fibrils and aggregates of Aβ is shown in the cultivation of human neurons in conditions of 3D-culture based on hydrogels (Kwak et al, 2020). This result is explained by the effect of adhesion receptors cadherins and integrins on the release of Aβ (Biose et al, 2023).…”

Sildenafil as a Candidate Drug for Alzheimer’s Disease: Real-World Patient Data Observation and Mechanistic Observations from Patient-Induced Pluripotent Stem Cell-Derived Neurons

“…Likewise, various integrins signaling pathway genes and gene families (collagens (COL), integrins (ITG), FYN, PIK3C2B, MAP3K5, FLNB, ACTN1, LAMA1) were found to be dysregulated after sildenafil treatment. Integrins are critical signaling receptors, which mediate cell-cell communication and contribute to cognitive functions particularly in synaptic transmission [51]. This signaling pathway is known to have pathophysiological role in neurodevelopment, plasticity, and central nervous system (CNS) diseases [51][52][53].…”

“…Integrins are critical signaling receptors, which mediate cell-cell communication and contribute to cognitive functions particularly in synaptic transmission [51]. This signaling pathway is known to have pathophysiological role in neurodevelopment, plasticity, and central nervous system (CNS) diseases [51][52][53]. Also, integrin signaling is known to mediate A␤-induced neurotoxicity [54].…”