**4.2. Novel treatment approaches**

Molecular chaperones play important roles in protein homeostasis. It was reported that inhibiting heat shock protein 90 (Hsp90) could inhibit tau toxicity in tauopathy model [160]. The mechanism behind could involve Hsp90 stabilize p35, the activator of CDK5, GSK3β, and tau, inhibiting their degradation [160, 161]. On the other hand, Hsp70 could facilitate protein ubiquitination and degradation by the proteasome [162]. Overexpression of Hsp70 in cells could decrease tau aggregation in vitro [163]. Recently, it is also suggested that targeting cochaperones of Hsp90 could offer another approach to ameliorate tauopathy [164].

Several traditional Chinese medicines have been suggested that might be useful for treating tauopathies [150, 165]. Huannao Yicong Decotion was shown to improve learning and memory in rat AD model. Immunolabeling showed the expression levels of GSK3β, CDK5, and TTBK1 in CA1 region of the hippocampus are downregulated in the drug treatment groups [150]. Interestingly, it was also suggested that some traditional Chinese medicines, including Huperzine A and Tianma, could induce upregulation of ubiquitin ligases, indicating that they might facilitate protein degradation through ubiquitin-proteasome pathway [166].
