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• W2000936337 endingPage "596" @default.
• W2000936337 startingPage "591" @default.
• W2000936337 abstract "Autophagy (macroautophagy) is an evolutionally conserved process by which cytoplasmic proteins and organelles are surrounded by unique double membranes and are subsequently degraded upon fusion with lysosomes. Many autophagy-related genes (Atg) have been identified in yeast; a ubiquitin-like Atg12-Atg5 system is also essential for the elongation of the isolation membrane in mammalian cells. Nevertheless, the regulation of autophagy in neurons remains largely unknown. In this study, we crossed conditional knockout mice Atg5flox/flox with pcp2-Cre transgenic mice, which express Cre recombinase through a Purkinje cell–specific promoter, pcp2. In Atg5flox/flox; pcp2-Cre mice, the Atg5 gene was excised as early as postnatal day 6; Purkinje cells started to degenerate after approximately 8 weeks, and the animals showed an ataxic gait from around 10 months. Initially, however, the Purkinje cells showed axonal swelling around its terminals from as early as 4 weeks after birth. An electron microscopic analysis revealed the accumulation of autophagosome-like double-membrane structures in the swollen regions, together with numerous membranous organelles, such as tubular or sheet-like smooth endoplasmic reticulum and vesicles. These results suggest that Atg5 plays important roles in the maintenance of axon morphology and membrane structures, and its loss of function leads to the swelling of axons, followed by progressive neurodegeneration in mammalian neurons." @default.
• W2000936337 created "2016-06-24" @default.
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• W2000936337 date "2007-11-26" @default.
• W2000936337 modified "2023-10-15" @default.
• W2000936337 title "Aberrant Membranes and Double-Membrane Structures Accumulate in the Axons of<i>Atg5</i>-Null Purkinje Cells before Neuronal Death" @default.
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• W2000936337 doi "https://doi.org/10.4161/auto.4964" @default.
• W2000936337 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/17912025" @default.
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