Sex and region-specific disruption of autophagy and mitophagy in Alzheimer’s disease: linking cellular dysfunction to cognitive decline

Cell Death Discovery, Journal Year: 2025, Volume and Issue: 11(1)

Published: April 26, 2025

Abstract Macroautophagy and mitophagy are critical processes in Alzheimer’s disease (AD), yet their links to behavioral outcomes, particularly sex-specific differences, not fully understood. This study investigates autophagic (LC3B-II, SQSTM1) mitophagic (BNIP3L, BNIP3, BCL2L13) markers the cortex hippocampus of male female 3xTg-AD mice, using western blotting, transmission electron microscopy (TEM), tests (novel object recognition novel placement). Significant differences emerged: mice exhibited autophagosome accumulation due impaired degradation cortex, while males showed fewer autophagosomes, especially hippocampus, without significant changes. TEM analyses demonstrated variations mitochondrial mitophagosome numbers correlated with memory outcomes. Females had enhanced mitophagy, higher BNIP3L BCL2L13 levels, whereas elevated BNIP3 dimers. Cognitive deficits females dysfunction males, LC3B-II levels associated positively cognitive performance, suggesting protective autophagy effects. Using machine learning, we predicted based on data, pioneering a predictive approach cellular outcomes AD. These findings underscore importance regulation AD support personalized therapeutic approaches targeting these pathways. Integrating learning emphasizes its potential advance neurodegenerative research.

Language: Английский

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BCL2L13 Influences Autophagy and Ceramide Metabolism without Affecting Temozolomide Resistance in Glioblastoma

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 26, 2024

Abstract Temozolomide (TMZ) resistance in glioblastoma (GB) poses a significant therapeutic challenge. We developed TMZ-resistant (TMZ-R) U251 GB model, revealing distinct differences cell viability, apoptosis, autophagy, and lipid metabolism between TMZ-R non-resistant (TMZ-NR) cells. TMZ-NR cells exhibited heightened sensitivity to TMZ-induced while cells-maintained viability. Autophagy flux was completely inhibited cells, indicated by LC3βII SQSTM1 accumulation. BCL2L13, which showed higher expression demonstrated increased interaction with Ceramide Synthase 6 (CerS6) reduced 2 (CerS2) BCL2L13 knockdown (KD) disrupted autophagy flux, decreasing autophagosome accumulation increasing it These changes contributed altered ceramide profiles, where displayed elevated levels of Cer 16:0, 18:0, 20:0, 22:0, 24:0, 24:1. Our findings highlight as potential targets overcome TMZ GB.

Language: Английский

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Sex and Region-Specific Disruption of Autophagy and Mitophagy in Alzheimer's Disease: Linking Cellular Dysfunction to Cognitive Decline

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 31, 2024

Abstract Macroautophagy and mitophagy are critical processes in Alzheimer’s disease (AD), yet their links to behavioral outcomes, particularly sex-specific differences, not fully understood. This study investigates autophagy (LC3B-II, SQSTM1) (BNIP3L, BNIP3, BCL2L13) markers the cortex hippocampus of male female 3xTg-AD mice, using western blotting, transmission electron microscopy (TEM), tests (novel object recognition novel placement). Significant differences emerged: mice exhibited autophagosome accumulation due impaired degradation cortex, while males showed fewer autophagosomes, especially hippocampus, without significant changes. TEM analyses demonstrated variations mitochondrial mitophagosome numbers correlated with memory outcomes. Females had enhanced mitophagy, higher BNIP3L BCL2L13 levels, whereas elevated BNIP3 dimers. Cognitive deficits females dysfunction males, LC3B-II levels associated positively cognitive performance, suggesting protective effects. Using machine learning, we predicted based on data, pioneering a predictive approach cellular outcomes AD. These findings underscore importance regulation AD support personalized therapeutic approaches targeting these pathways. Integrating learning emphasizes its potential advance neurodegenerative research. Figure Graphical Sex-specific (AD) highlighted. Female show deficits, exhibit behavior.

Language: Английский

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NRF-Mediated Autophagy and UPR: Exploring New Avenues to Overcome Cancer Chemo-Resistance

European Journal of Pharmacology, Journal Year: 2024, Volume and Issue: unknown, P. 177210 - 177210

Published: Dec. 1, 2024

Language: Английский

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