Septin6 as a new approach for AD treatment

The number of Alzheimer’s disease (AD) patients is increasing and new therapeutic approaches need to be proposed urgently. In recent years, some researchers have focused on the relationship between calcium homeostasis and AD; however, selective regulation of abnormal calcium signaling pathways and related targets of action remain unclear, presenting a challenge. Gerard Griffioen’s team in Belgium has proposed a self-reinforcing amplification between cytoplasmic calcium concentration [Ca²⁺]_cyto and AD pathology in previous studies, discovering a new kind of smallmolecule scaffold protein. The protein, ReS19-T, can stabilize the structure of septin filaments and significantly improve the core pathology of AD by inhibiting the pathological activation of store-operated calcium entry (SOCE) and restoring calcium homeostasis, thereby suggesting a new avenue for therapeutic intervention. However, there is still a way to go before clinical application. There are some questions. SEP2/6/7 hexamer plays a role in maintaining immune function, so could ReS19-T affect this function and impact immune responses? Moreover, both Stim1 and Orai (affected by TRPC) contribute to SOCE. The TRPC-specific inhibitor SKF-96365 is highly selective, and its relationship with AD remains to be investigated. Future studies might use SKF-96365 to validate the therapeutic effect of Res19-T. In conclusion, Septin6 as a new approach to AD treatment expects more relevant research to emerge.