Mutations in the macroautophagy/autophagy gene WDR45 cause β-propeller protein-associated neurodegeneration (BPAN); however the molecular and cellular mechanism of the disease process is largely unknown. Here we generated constitutive wdr45 knockout (KO) mice that displayed cognitive impairments, abnormal synaptic transmission and lesions in several brain regions. Immunohistochemistry analysis showed loss of neurons in prefrontal cortex and basal ganglion in aged mice, and increased apoptosis in prefrontal cortex, recapitulating a hallmark of neurodegeneration. Quantitative proteomic analysis showed accumulation of endoplasmic reticulum (ER) proteins in KO mouse. At the cellular level, accumulation of ER proteins due to WDR45 deficiency resulted in increased ER stress and impaired ER quality control. The unfolded protein response (UPR) was elevated through ERN1/IRE1 or EIF2AK3/PERK pathway, and eventually led to neuronal apoptosis. Suppression of ER stress or activation of autophagy through MTOR inhibition alleviated cell death. Thus, the loss of WDR45 cripples macroautophagy machinery in neurons and leads to impairment in organelle autophagy, which provides a mechanistic understanding of cause of BPAN and a potential therapeutic strategy to treat this genetic disorder.

A facile magnetic solid phase extraction (MSPE) of aflatoxins (AFs) from liquid samples was developed using polydopamine-coated magnetic nanoparticles (PD-MNPs) as the adsorbent. PD-MNPs were prepared from amine-terminated MNPs and dopamine via an in situ oxidative self-polymerization approach. Under the selected MSPE conditions, extraction yields ranging from 59.3% for AF G₂ to 89.0% for AF B₁ were obtained with good repeatability. Coupled with HPLC-MS/MS quantification, the MSPE procedure serves not only for sample cleanup but also for AFs enrichment that is highly desired for trace analysis. The proposed MSPE-HPLC-MS/MS method had a linear calibration curve in the concentration range from 0.00600 to 3.00 ng/mL aflatoxin and limits of detection of 0.0012 ng/mL for AF B₁, AF B₂, and AF G₁, and 0.0031 ng/mL for AF G₂.