Biochemical and Biophysical Research Communications, Journal Year: 2024, Volume and Issue: 747, P. 151254 - 151254
Published: Dec. 27, 2024
Language: Английский
Biochemical and Biophysical Research Communications, Journal Year: 2024, Volume and Issue: 747, P. 151254 - 151254
Published: Dec. 27, 2024
Language: Английский
bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown
Published: Dec. 17, 2024
Abstract Beta-propeller Protein Associated Neurodegeneration (BPAN) is a devastating neurodevelopmental and neurodegenerative disease linked to variants in WDR45 . Currently, there no cure or altering treatment for this disease. This is, part, due lack of insight into early phenotypes BPAN progression ’s role establishing maintaining neurological function. Here we generated characterized mouse model bearing c52C>T patient variant Wdr45. We show mutation ablates protein expression alters autophagy the brain. Behavioral analysis these mice revealed characteristic signs including cognitive impairment, hyperactivity, motor decline. behaviors coincide with widespread neuroinflammation development axonal spheroids multiple neuron subclasses throughout Several lines evidence suggest arise from axon terminals. Transcriptomic uncovered disrupted pathways cortex genes associated synapses, neurites, endosomes, endoplasmic reticulum, ferroptosis. supported by accumulation iron regulating transferrin receptor 1 (TFRC) reticulum resident calreticulin (CALR) as animals age. CALR forms spheroid structures similar seen animals. Taken together, our data demonstrate that necessary healthy brain function maintenance opens door therapeutics targeting further exploration neuronal
Language: Английский
Citations
0Trends in Cell Biology, Journal Year: 2024, Volume and Issue: unknown
Published: Dec. 1, 2024
Language: Английский
Citations
0Journal of Basic Microbiology, Journal Year: 2024, Volume and Issue: unknown
Published: Dec. 25, 2024
ABSTRACT Autophagy regulates the development of Candida albicans ( C. ) biofilms and their sensitivity to antifungals. Atg1, a serine/threonine protein kinase, recruits autophagy‐related proteins for autophagosome formation. Atg9, only transmembrane protein, is phosphorylated by Atg1 during autophagy. The specific roles Atg9 in biofilm formation resistance remain unclear. study used RT‐ q PCR Western blotting assess correlation between , formation, XTT reduction assays evaluate antifungal resistance, commercial kits detect reactive oxygen species (ROS), mitochondrial membrane potential (MMP), autophagy activity, transmission electron microscopy (TEM) morphological changes, protein–protein interaction (PPI) analysis analyze Atg9. Results demonstrated that were highly expressed than planktonic cells. Biofilm MMP activity decreased ROS increased atg1 Δ/Δ atg9 Δ/Δ. TORC1 inhibition with rapamycin rescued reduced PPI TEM observation indicated interacted which was certified blotting. This suggested interacts activates regulating biofilms.
Language: Английский
Citations
0Biochemical and Biophysical Research Communications, Journal Year: 2024, Volume and Issue: 747, P. 151254 - 151254
Published: Dec. 27, 2024
Language: Английский
Citations
0