Immune Mechanisms in Alzheimer’s Disease: The Role of Toll-Like Receptors Signalling

• Published in: Current pharmacology reports Vol. 10; no. 6; pp. 267 - 276
• Main Authors: Sharma, Dinisha, Manjunatha, P. M., Babu, T. Hari, Dhungel, Arpan, Swaraj, Sushree, Janadari, Suresh, Sharma, Uday Raj, Surendra, V., Taj, Nageena, Gayathri, S. V.
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.12.2024
• Subjects: Biomedical and Life Sciences; Biomedicine; Cancer Research; Diabetes and Diabetes Complications; Mental Health; Molecular Medicine; Neuropharmacology; Pharmacology/Toxicology; Review; Topical Collection on Healthy Aging; Neuroinflammation; Toll like receptor; Amyloid beta; Alzheimer’s disease; Cytokines; Neurodegeneration
• ISSN: 2198-641X; 2198-641X
• DOI: 10.1007/s40495-024-00376-w

Purpose of Review This comprehensive review aims to explore into the origins of Alzheimer’s disease (AD) a debilitating disorder that primarily affects the cortical and limbic regions of the human brain. We will explore the development of AD including tangles, Aβ plaques, neuroinflammation, oxidative stress and cholinergic dysfunction. Additionally, we will focus on the emerging understanding of how the brains immune mechanisms, microglia and astrocyte receptors play a role, in triggering an immune response that impacts disease progression. Recent Findings Microglia, which possess a range of cell surface receptors like TLRs, integrin, SCARA1, CD14, 36 and 47 play a role in this process. Particularly noteworthy are TLRs due to their ability to detect types of DAMPs and PAMPs including Aβ peptides. Activating TLR signalling pathways can have both effects like enhancing the uptake of Aβ plaques and negative consequences such as triggering the production of inflammatory cytokines. These recent discoveries highlight the potential, for targeted interventions that focus on TLRs, especially TLR2 and TLR4 to influence the progression of AD. Summary Alzheimer’s disease origin lies in complex cellular and molecular pathways. While neurofibrillary tangles, Aβ plaques, neuroinflammation, oxidative stress, and cholinergic dysfunction have long been recognized as key factors in AD development, recent research highlights the critical role of the brain’s immune system. Microglia, equipped with various receptors, especially TLRs, play a central role in this immune response by detecting molecules like Aβ peptides. Targeting TLRs, particularly TLR2 and TLR4, holds promise for intervening in AD, potentially altering disease progression and deepening our understanding of this devastating neurodegenerative disorder.