Recently, necroptosis, as a programmed cell death pathway, has drawn much attention as it has been implicated in multiple pathologies, especially in the field of inflammatory diseases. Pseudokinase mixed lineage kinase domain-like protein (MLKL) serves as a terminal-known obligate effector in the process of necroptosis. To date, the majority of research on MLKL has focused on its role in necroptosis, and the prevailing view has been that the sole function of MLKL is to mediate necroptosis. However, increasing evidence indicates that MLKL can serve as a regulator of many diseases via its non-necroptotic functions. These functions of MLKL shed light on its functional complexity and diversity. In this review, we briefly introduce the current state of knowledge regarding the structure of MLKL, necroptosis signaling, as well as cross-linkages among necroptosis and other regulated cell death pathways, and we particularly highlight recent progress related to newly identified functions and inhibitors of MLKL. These discussions promote a better understanding of the role of MLKL in diseases, which will foster efforts to pharmacologically target this molecule in clinical treatments.

As one of the most densely innervated tissues, the dental pulp contains abundant nerve fibres, including sensory, sympathetic and parasympathetic nerve fibres. Studies in animal models and human patients with pulpitis have revealed distinct alterations in protein expression and histological appearance in all types of dental nerve fibres. Various molecules secreted by neurons, such as classical neurotransmitters, neuropeptides and amino acids, not only contribute to the induction, sensitization and maintenance of tooth pain, but also regulate non-neuronal cells, including fibroblasts, odontoblasts, immune cells and vascular endothelial cells. Dental nerves are particularly important for the microcirculatory and immune responses in pulpitis via their release of a variety of functional substances. Further, nerve fibres are found to be involved in dental soft and hard tissue repair. Thus, understanding how dental nerves participate in pulpitis could have important clinical ramifications for endodontic treatment. In this review, the roles of dental nerves in regulating pulpal inflammatory processes are highlighted and their implications for future research on this topic are discussed.

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