Synaptic plasticity enhances or reduces connections between neurons, affecting learning and memory. Postsynaptic AMPARs mediate greater than 90% of the rapid excitatory synaptic transmission in glutamatergic neurons. The number and subunit composition of AMPARs are fundamental to synaptic plasticity and the formation of entire neural networks. Accordingly, the insertion and functionalization of AMPARs at the postsynaptic membrane have become a core issue related to neural circuit formation and information processing in the central nervous system. In this review, we summarize current knowledge regarding the related mechanisms of AMPAR expression and trafficking. The proteins related to AMPAR trafficking are discussed in detail, including vesicle-related proteins, cytoskeletal proteins, synaptic proteins, and protein kinases. Furthermore, significant emphasis was placed on the pivotal role of the actin cytoskeleton, which spans throughout the entire transport process in AMPAR transport, indicating that the actin cytoskeleton may serve as a fundamental basis for AMPAR trafficking. Additionally, we summarize the proteases involved in AMPAR post-translational modifications. Moreover, we provide an overview of AMPAR transport and localization to the postsynaptic membrane. Understanding the assembly, trafficking, and dynamic synaptic expression mechanisms of AMPAR may provide valuable insights into the cognitive decline associated with neurodegenerative diseases.

The microbiota-gut-brain axis has attracted significant attention with respect to studying the mechanisms of brain aging; however, the specific connection between gut microbiota and aging remains unclear. The abnormal expression and mutation of proteins belonging to the P4-ATPase family, including Atp11b, results in a variety of neurological diseases. The results of our analysis demonstrate that there was a shift in the abundance of certain gut microbiota in Atp11b-knockout (KO) mice. Specifically, there was an increase in pro-inflammatory bacteria that accelerate aging and a decrease in probiotics that delay aging. Consequently, an enhanced oxidative stress response was observed, which was characterized by a reduction in the superoxide dismutase (SOD) activity and an increase in malondialdehyde (MDA) and reactive oxygen species (ROS) levels. In addition, our data demonstrate that there was a decrease in the number of cells in the dentate gyrus (DG) region of the hippocampus, and aggravation of aging-related pathological features such as senescence β-galactosidase (SA-β-Gal), p-HistoneH2AX (Ser139), and p16^INK4. Moreover, KO mice show typical aging-associated behavior, such as memory impairment and slow pain perception. Taken together, we demonstrate a possible mechanism of aging induced by gut microbiota in Atp11b-KO mice, which provides a novel perspective for the treatment of aging through the microbiota-gut-brain axis.

The delay in wound healing caused by chronic wounds or pathological scars is a pressing issue in clinical practice, imposing significant economic and psychological burdens on patients. In particular, with the aging of the population and the increasing incidence of diseases such as diabetes, impaired wound healing is one of the growing health problems. MicroRNA (miRNA) plays a crucial role in wound healing and regulates various biological processes. Our results show that miR–618 was significantly upregulated during the inflammatory phase of wound healing.Subsequently, miR–618 promotes the secretion of pro–inflammatory cytokines and regulates the proliferation and migration of keratinocytes. Mechanistically, miR–618 binds to the target gene–Atp11b and inhibits the PI3K–Akt signaling pathway, inhibiting the epithelial–mesenchymal transition (EMT) of keratinocytes. In addition, the PI3K–Akt signaling pathway induces the enrichment of nuclear miR–618, and miR–618 binds to the promoter of Lin7a to regulate gene transcription. Intradermal injection of miR–618 antagomir around full–thickness wounds in peridermal mice effectively accelerates wound closure compared to control. In conclusion, miR–618 antagomir can be a potential therapeutic agent for wound healing.