Exploring the vital role of microglial membrane receptors in Alzheimer’s disease pathogenesis: a comprehensive review

Neurodegenerative diseases constitute a broad category of diseases caused by the degeneration of the neurons.They are mainly manifested by the gradual loss of neuron structure and function and eventually can cause death or loss of neurons.As the global population ages rapidly, increased people are being diagnosed with neurodegenerative diseases.It has been established that the onset of Alzheimer's disease (AD) is closely linked with increasing age and its major pathological features include amyloid-beta plaques (Aβ), Tau hyperphosphorylation, Neurofibrillary tangles (NFTs), neuronal death as well as synaptic loss.The involvement of microglia is crucial in the pathogenesis and progression of AD and exhibits a dual role.For instance, in the early stage of AD, microglia surface membrane proteins or receptors can participate in immunophagocytosis, and anti-inflammatory functions and act as a physical barrier after recognizing various ligands such as Aβ and NFTs.However, in the later stage of the disease, membrane receptors on the surface of microglia can cause its activation to release a substantial quantity of pro-inflammatory factors.Which can amplify the neuroinflammatory response.The rapid decline of normal immune phagocytosis can result in the continuous accumulation of abnormal proteins, leading to neuronal dysfunction and destruction of the formed physical barrier as well as the neurovascular microenvironment.It can also increase the transformation of microglia from anti-inflammatory phenotype M2 to pro-inflammatory phenotype M1, induce severe neuronal injury or apoptosis, and aggravate the progression of AD.Due to few articles have focused on the AD-related membrane protein receptors on microglia, thus in this paper, we have reviewed several representative microglial membrane proteins or receptors about their specific roles and functions implicated in AD, and expect that there will be more indepth research and scientific research results in the treatment of AD by targeted regulation of microglia membrane protein receptors in the future.