Fig. 7.

Decreased cellular cholesterol by DHCR24 knockdown contributes to astrocytic tau pathology in C8D1A cells. DHCR24 knockdown in C8D1a astrocytes leads to inhibition of cholesterol synthesis and deficiency of cholesterol in the plasma membrane. Meanwhile, reduced membrane cholesterol decreases the cavin-1 expression level, resulting in the disruption of caveolae. Moreover, the impairment of caveolae construction leads to the altered nanoclustering of Ras that locates in this platform and causes its overactivation, then the MAPK/ERK signaling pathway is activated. Eventually, activated ERK1/2 promotes tau hyperphosphorylation