Figure 8 | Scientific Reports

Figure 8

From: ESCRT-0 dysfunction compromises autophagic degradation of protein aggregates and facilitates ER stress-mediated neurodegeneration via apoptotic and necroptotic pathways

Figure 8

Schematic presentation of neuronal cell death induced by ESCRT-0/Hrs dysfunction.

Loss of Hrs leads to a vicious cycle of autophagic impairment and ER stress, which induces the activation of downstream MKK4-JNK signaling and subsequent caspase-dependent apoptosis, which can be attenuated by pan-caspase inhibitors. Alternatively, activation of the ER stress response induces necroptosis through activation of the RIPK1/RIPK3-JNK signaling cascade. This process can be restored by pharmacological or genetic suppression of RIPK1.

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