Fig. 6: Proposed schematic diagram of APOE3 and APOE4 RCMs in the clearance of myelin debris from demyelinated SGNs. | Cell Death Discovery

Fig. 6: Proposed schematic diagram of APOE3 and APOE4 RCMs in the clearance of myelin debris from demyelinated SGNs.

From: APOE4 impairs macrophage lipophagy and promotes demyelination of spiral ganglion neurons in mouse cochleae

Fig. 6

The five-step process of Myelin debris clearance: ① Following axonal demyelination of SGNs, myelin debris is phagocytosed and internalized by RCMs. ② The phagocytosed myelin debris is degraded into cholesterol through the lysosomal degradation pathway. ③ A portion of the cholesterol is effluxed from RCMs and reused by Schwann cells to form new myelin sheaths. ④ The remained intracellular cholesterol is used for LDs synthesis. ⑤ LDs are degraded through the lipophagy pathway. APOE3 RCMs could efficiently phagocytose myelin debris (step ①) and maintain the LDs homoeostasis via step ②-⑤. On the contrary, APOE4 RCMs exhibit impaired phagocytic ability for myelin debris clearance (step ①). In addition, APOE4 RCMs showed a defect lipophagy, resulting in abnormal accumulation of LDs (step ④ and ⑤), which could synthetically impair the myelin debris clearance by RCMs and diminish the reused cholesterol in repairment of demyelinated lesions of SGNs.

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