Beta-propeller protein-associated neurodegeneration (BPAN) is caused by mutations in the autophagy gene WDR45/WIPI4. In human, BPAN is associated with static encephalopathy in childhood and neurodegeneration in adulthood (SENDA). It has been proposed that WDR45 mutations cause neurodegeneration due to defective autophagy. Whether these mutations cause a global attenuation or a defect in a subset of autophagy functions is unknown. Based on a recent study showing that wdr45 knockout mice exhibit defective autophagy associated with an increased ER stress, we propose that ER-mediated autophagy, a selective activation of autophagy, is defective in mouse and cellular models of BPAN. We discuss the implication of these findings on the pathophysiological relevance of the relationship between ER stress and autophagy in BPAN as well as other neurodegenerative diseases exhibiting ER stress and defective autophagy.
Keywords: Autophagy; BPAN; ER stress; beta propeller associated neurodegeneration; neurodegeneration.