Toll-Like Receptor 4: A Promising Therapeutic Target for Alzheimer’s Disease
Linyu Wu, Xiao‐Hui Xian, Guangyu Xu, Zixuan Tan, Fang Dong, Min Zhang, Feng Zhang
Abstract
Alzheimer’s disease (AD) is a progressive neurodegenerative disease that primarily manifests as memory deficits and cognitive impairment and has created health challenges for patients and society. In AD, amyloid β-protein (Aβ) induces Toll-like receptor 4 (TLR4) activation in microglia. Activation of TLR4 induces downstream signaling pathways and promotes the generation of proinflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β), which also trigger the activation of astrocytes and influence amyloid-dependent neuronal death. Therefore, TLR4 may be an important molecular target for treating AD by regulating neuroinflammation. Moreover, TLR4 regulates apoptosis, autophagy, and gut microbiota and is closely related to AD. This article reviews the role of TLR4 in the pathogenesis of AD and a range of potential therapies targeting TLR4 for AD. Elucidating the regulatory mechanism of TLR4 in AD may provide valuable clues for developing new therapeutic strategies for AD.