Ryanodine Receptors: A Potential Treatment Target in Various Neurodegenerative Disease

Progressive neuronal demise is a key contributor to the key pathogenic event implicated in many different neurodegenerative disorders (NDDs). There are several therapeutic strategies available; however, none of them are particularly effective. Targeted neuroprotective therapy is one such therapy, which seems a compelling option, yet remains challenging due to the internal heterogeneity of the mechanisms underlying various NDDs. An alternative method to treat NDDs is to exploit common modalities involving molecularly distinct subtypes and thus develop specialized drugs with broad-spectrum characteristics. There is mounting evidence which supports for the theory that dysfunctional ryanodine receptors (RyRs) disrupt intracellular Ca(2+)homeostasis, contributing to NDDs significantly. This review aims to provide direct and indirect evidence on the intersection of NDDs and RyRs malfunction, and to shed light on novel strategies to treat RyRs-mediated disease, modifying pharmacological therapies such as the potential therapeutic role of dantrolene, a RyRs antagonist.

Automated summary

Progressive neuronal demise plays a crucial role in various neurodegenerative disorders, with limited and challenging therapeutic strategies available. Developing broad-spectrum drugs based on common mechanisms may offer an alternative approach for treating NDDs, while emerging research highlights the significance of dysfunctional ryanodine receptors in NDDs and proposes novel therapeutic strategies.