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

Aida Adlimoghaddam,

Fariba Fayazbakhsh, Mohsen Mohammadi

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Окт. 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.

Язык: Английский

Targeting the Interplay Between Autophagy and the Nrf2 Pathway in Parkinson’s Disease with Potential Therapeutic Implications DOI Creative Commons
Mengru Liu, Siqi Liu, Zi-Han Lin

и другие.

Biomolecules, Год журнала: 2025, Номер 15(1), С. 149 - 149

Опубликована: Янв. 19, 2025

Parkinson’s disease (PD) is a prevalent neurodegenerative disorder marked by the progressive degeneration of midbrain dopaminergic neurons and resultant locomotor dysfunction. Despite over two centuries recognition as chronic disease, exact pathogenesis PD remains elusive. The onset progression involve multiple complex pathological processes, with dysfunctional autophagy elevated oxidative stress serving critical contributors. Notably, emerging research has underscored interplay between in pathogenesis. Given limited efficacy therapies targeting either dysfunction or stress, it crucial to elucidate intricate mechanisms governing their develop more effective therapeutics. This review overviews role nuclear factor erythroid 2-related 2 (Nrf2), pivotal transcriptional regulator orchestrating cellular defense against these processes. By elucidating key processes PD, this will deepen our comprehensive understanding multifaceted underlying may uncover potential strategies for its prevention treatment.

Язык: Английский

Процитировано

3

Lactate Mediates Exercise-Induced Modulation of Mitophagy and Ferroptosis, Reducing Amyloid-Beta and Tau in Type 2 Diabetes: A Molecular Study DOI
Kayvan Khoramipour,

Pouria Khosravi,

Fereshteh Shahidi

и другие.

Опубликована: Янв. 1, 2025

Background: This study examined the impact of lactate accumulation, induced by high-intensity interval training (HIIT), on reducing amyloid-beta (Aβ) and tau protein levels through enhanced mitophagy decreased ferroptosis in hippocampus type 2 diabetic rats.Methods: Thirty-two male Wistar rats were divided into four groups: control (Co), exercise (EX), diabetes (DB), with (DB + EX). Diabetes was DB EX groups via a high-fat diet followed streptozotocin injection (35 mg/kg). The performed treadmill-based HIIT, involving 4–10 running intervals at 80–100% Vmax. Serum hippocampal expression MCT2, SIRT1, BDNF, p62, Keap1, NRF2, MDA, GPX4, PINK1, parkin, Aβ, Tau assessed.Results: In group, Parkin elevated, while reduced compared to group.Conclusion: HIIT enhances reduces lactate-SIRT1-BDNF p62-Keap1-NRF2 pathways, potentially mitigating Aβ accumulation.

Язык: Английский

Процитировано

0

LncRNA TCONS_00067339 as a key regulatory factor inducing decreased cell viability and ferroptosis in neonatal hypoxic-ischemic brain damage DOI
Y. Li,

Junfang Sun,

Chun-Chi Lai

и другие.

Brain Research, Год журнала: 2025, Номер 1854, С. 149562 - 149562

Опубликована: Март 8, 2025

Язык: Английский

Процитировано

0

Ferroptosis and hyperoxic lung injury: insights into pathophysiology and treatment approaches DOI Creative Commons

Xiaoqiong Zhou,

Lei Tian, Zongde Zhang

и другие.

Frontiers in Pharmacology, Год журнала: 2025, Номер 16

Опубликована: Март 18, 2025

Hyperoxia therapy is a critical clinical intervention for both acute and chronic illnesses. However, prolonged exposure to high-concentration oxygen can cause lung injury. The mechanisms of hyperoxic injury (HLI) remain incompletely understood, current treatment options are limited. Improving the safety hyperoxia has thus become an urgent priority. Ferroptosis, novel form regulated cell death characterized by iron accumulation excessive lipid peroxidation, been implicated in pathogenesis HLI, including diffuse alveolar damage, vascular endothelial injury, bronchopulmonary dysplasia. In this review, we analyze latest findings on ferroptosis therapeutic strategies HLI. Our aim provide new insights HLI facilitate translation these from bench bedside.

Язык: Английский

Процитировано

0

Nebulized M2 macrophage-derived nanovesicles for the treatment of explosion-induced acute lung injury DOI

Linqiang Tian,

Jie Jin,

Feng Lai

и другие.

Journal of Colloid and Interface Science, Год журнала: 2025, Номер unknown, С. 137381 - 137381

Опубликована: Март 1, 2025

Язык: Английский

Процитировано

0

Complexin 2 contributes to the protective effect of NAD+ on neuronal survival following neonatal hypoxia-ischemia DOI

Xiaowen Xu,

Xiuwen Zhou, Li Zhang

и другие.

Acta Pharmacologica Sinica, Год журнала: 2025, Номер unknown

Опубликована: Апрель 17, 2025

Язык: Английский

Процитировано

0

The associations between brain aging and mitochondria dysfunction: Mechanism and intervention strategies DOI
Yi Rong

Deleted Journal, Год журнала: 2025, Номер unknown, С. 1 - 16

Опубликована: Апрель 20, 2025

Brain aging, an exquisitely intricate biological phenomenon, is intertwined with cognitive deterioration and the pathogenesis of neurodegenerative maladies. Mitochondria, cellular powerhouses responsible for energy homeostasis, assume a central indispensable role in this process. This review delves deeply into multifaceted associations between mitochondrial dysfunction brain encompassing perturbations metabolism, exacerbation oxidative stress, aberrations dynamics, activation inflammatory response, DNA mutations, all which interact complex network to drive progression aging. Simultaneously, it undertakes meticulous dissection functions some key mitochondria-related molecules In terms intervention strategies, emerging evidence suggests that inhibition cyclic GMP-AMP synthase-stimulator interferon genes (cGAS-STING) signaling axis holds promise alleviating phenotypes senescent cells tissues. Downregulating levels relevant transfer RNA-derived small RNAs (tsRNAs) represents potential approach safeguard crucial processes. Supplementation spermidine spermine has demonstrated efficacy ameliorating function performance. Moreover, comprehensive paradigms targeting antioxidative stress responses, autophagy regulation offer avenues retarding Collectively, existing body research furnishes profound insights underlying mechanisms aging serves as bedrock development efficacious modalities. Future imperatives should center on elucidating molecular mechanisms, formulating highly precise expediting translation basic findings clinical applications. utmost significance enhancing quality life elderly forestalling onset diseases.

Язык: Английский

Процитировано

0

Nuclear factor erythroid 2-related factor-mediated signaling alleviates ferroptosis during cerebral ischemia-reperfusion injury DOI Open Access
Zheng Li, Jihong Xing

Biomedicine & Pharmacotherapy, Год журнала: 2024, Номер 180, С. 117513 - 117513

Опубликована: Сен. 27, 2024

Язык: Английский

Процитировано

2

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

Aida Adlimoghaddam,

Fariba Fayazbakhsh, Mohsen Mohammadi

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Окт. 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.

Язык: Английский

Процитировано

1