| Literature DB >> 26000824 |
Yan G Zhao1, Le Sun, Guangyan Miao, Cuicui Ji, Hongyu Zhao, Huayu Sun, Lin Miao, Saori R Yoshii, Noboru Mizushima, Xiaoqun Wang, Hong Zhang.
Abstract
WDR45/WIPI4, encoding a WD40 repeat-containing PtdIns(3)P binding protein, is essential for the basal autophagy pathway. Mutations in WDR45 cause the neurodegenerative disease β-propeller protein-associated neurodegeneration (BPAN), a subtype of NBIA. We generated CNS-specific Wdr45 knockout mice, which exhibit poor motor coordination, greatly impaired learning and memory, and extensive axon swelling with numerous axon spheroids. Autophagic flux is defective and SQSTM1 (sequestosome-1)/p62 and ubiquitin-positive protein aggregates accumulate in neurons and swollen axons. Nes-Wdr45(fl/Y) mice recapitulate some hallmarks of BPAN, including cognitive impairment and defective axonal homeostasis, providing a model for revealing the disease pathogenesis of BPAN and also for investigating the possible role of autophagy in axon maintenance.Entities:
Keywords: ACTB, β-actin; AMC, aminomethylcoumarin; Atg, autophagy-related; BPAN, β-propeller protein-associated neurodegeneration; CALB, calbindin; CNS, central nervous system; DCN, deep cerebellar nuclei; Ei24, etoposide-induced gene 24; GFAP, glial fibrillary acid protein; H&E, hematoxylin and eosin; KO, knockout; LC3, microtubule-associated protein 1 light chain 3; LTP, long-term potentiation; MBP, myelin basic protein; NBIA, neurodegeneration with brain iron accumulation; RBFOX3, RNA binding protein, fox-1 homolog (C. elegans) 3; SENDA, static encephalopathy of childhood with neurodegeneration in adulthood; SQSTM1, sequestosome-1; WDR5/WIPI4, WD repeat domain 45; WT, wild type.; Wdr45/Wipi4; autophagy; axon swelling; epg, ectopic P granule; fEPSP, field excitatory postsynaptic potential; learning and memory; neurodegeneration; rpm, rotations per min
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Year: 2015 PMID： 26000824 PMCID： PMC4502681 DOI： 10.1080/15548627.2015.1047127
Source DB: PubMed Journal: Autophagy ISSN： 1554-8627 Impact factor: 16.016