Probing the therapeutic potential of TRPC6 for Alzheimer's disease in live neurons from patient-specific iPSCs

摘要

The induced pluripotent stem cells (iPSCs) offer an unprecedented opportunity to model and study Alzheimer's disease (AD) under patient-specific genetic background. The lower expression of transient receptor potential canonical 6 (TRPC6) was associated with AD patients, which might be involved in AD pathogenesis. However, the role of TRPC6 that played in AD process still needs more investigation in patient-relevant neurons. In this study, the iPSCs were generated from peripheral blood cells of sporadic AD patients and efficiently differentiated into mature cortical neurons. These sporadic AD-bearing neurons displayed higher levels of AD pathological markers A and phospho-tau, but lower levels of TRPC6, than those of control neurons. Treatment of AD neurons with TRPC6 protein fragment or agonist inhibited the elevation of A and phospho-tau. Our results in live AD neurons manifest that the compromised expression of TRPC6 substantially contributed to A pathology of sporadic AD, suggesting that targeting TRPC6 could help to develop novel therapeutic strategies for the treatments of AD.