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Additional file 1. Fig. S1. Schematic diagram of glioblastoma treatments. a Glioblastoma cells were treated with IR and UTMD in vitro. b Glioblastoma-bearing mice were treated with IR and UTMD in vivo. IR ionizing radiation, UTMD ultrasound-triggered microbubble destruction, 3-MA 3-methyladenine, BafA1 bafilomycin A1, PGRMC1 progesterone receptor membrane component 1, CTSB cathepsin B, CTSD cathepsin D, RAPA rapamycin, MBs microbubbles, GFP green fluorescent protein, RFP red fluorescent protein, CCK-8 cell counting kit-8, PI propidium iodide, LTG LysoTracker green fluorescent dye, US ultrasound. Fig. S2. Colony formation of glioblastoma cells was measured by clonogenic assay. GL261 and U251 cells were treated with 3-MA (5 mmol/L), BafA1 (10 nmol/L), AG-205 (10 ��mol/L), or RAPA (20 nmol/L) for 1 h followed by IR (2 Gy) or IR plus UTMD treatment for another 24 h. Moreover, GL261 and U251 cells were transfected with lentiviral vectors encoding AGT5 or PGRMC1. Then, cells were treated with UTMD followed by IR (2 Gy) exposure for another 24 h. The conlony formation of glioblastoma cells was measured by clonogenic assay. Values are expressed as mean �� SD (n = 3). *P

Neurofibrillary tangles of hyperphosphorylated tau protein (p-tau) are a key pathological feature of Alzheimer's disease (AD). Tau phosphorylation is suggested to be secondary to amyloid-beta (Aβ) accumulation. However,the mechanism by which Aβ induces tau phosphorylation in neurons remains unclear. Neurotrophin receptorp75 (p75NTR) is a receptor for Aβ and mediates Aβ neurotoxicity, implying that p75NTR may mediate Aβ-induced tau phosphorylation in AD. Here, we showed that Aβ-induced tau hyperphosphorylation and neurodegeneration,including tau phosphorylation, synaptic disorder and neuronal loss, in the brains of both male wild-type (Wt)mice and male P301L transgenic mice (a mouse model of human tauopathy) were alleviated by genetic knockout of p75NTR in the both mouse models. We further confirmed that the activation or inhibition of cyclin-dependent kinase 5 (CDK5) and glycogen synthase kinase-3β (GSK3β) significantly changed Aβ/p75NTR-mediated p-taulevels in neurons. Treatment of male P301L mice with soluble p75NTR extracellular domain (p75ECD-Fc), which antagonizes the binding of Aβ to p75NTR, suppressed tau hyperphosphorylation. Taken together, our findings suggest that p75NTR meditates Aβ-induced tau pathology and is a potential druggable target for AD and other tauopathies. Refereed/Peer-reviewed