Chuangxiong-Danggui Herb Pair Alleviated Cognitive Deficits of App/Ps1 Mice by Promoting Fundc1-Mediated Mitophagy

Published: Jan. 1, 2025

Background: Disruption of receptor-mediated mitophagy contributes to neuronal damage in AD. Chuangxiong-Danggui herb pair (CDHP) is classic herbal applied treating neurodegenerative diseases like AD, ALS, PD. Studies have indicated the neuroprotective effects CDHP, underlying mechanisms by which CDHP attenuates impairment AD remains be elucidated.PurposeThe objective this work was investigate anti-AD mechanism APP/PS1 mice mainly based on FUNDC1-mediated mitophagy.MethodsBehavioral assessments were conducted C57BL/6J and following treatment, alongside an evaluation morphology hippocampal region. In vitro, HT-22 cells induced Aβ25-35 before treated with CDHP. The investigated using transmission electron microscopy, Golgi staining, immunofluorescence, siRNA, Western blot analysis.ResultsResults from passive avoidance test MWM that significantly mitigated cognitive deficits mice, accompanied a reduction pathological CA1 CA3 regions hippocampus. Further testing found significant dendritic spines density rescued protein synaptophysin PSD-95 elevated group, while Aβ plaques deposition reduced. Simultaneously, markedly inhibits apoptosis decreased levels Cleaved Caspase-12 enhanced expression Bcl-2/Bax both vivo vitro. Additionally, improved mitochondrial function model decreasing abnormal mitochondria increasing COXIV. TEM results revealed clear mitophagy-autophagosomes nearly absent p62 LC3B treatment. Furthermore, increased FUNDC1 transgenic or AD-like cell model, luckily, it restoring II/I ratio vitro.ConclusionThe findings suggest dysfunction enhancing reduced injury.

Language: Английский

Predicting Which Mitophagy Proteins Are Dysregulated in Spinocerebellar Ataxia Type 3 (SCA3) Using the Auto-p2docking Pipeline

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(3), P. 1325 - 1325

Published: Feb. 4, 2025

Dysfunctional mitochondria are present in many neurodegenerative diseases, such as spinocerebellar ataxia type 3 (SCA3), also known Machado–Joseph disease (MJD). SCA3/MJD, the most frequent worldwide, is caused by abnormal expansion of polyglutamine tract (polyQ) at ataxin-3. This protein to deubiquitinate key proteins Parkin, which required for mitophagy. Ataxin-3 interacts with Beclin1 (essential initiating autophagosome formation adjacent mitochondria), well mitochondrial cristae TBK1. To identify other mitophagy pathway (according KEGG database) that can interact ataxin-3, here we developed a pipeline silico analyses protein–protein interactions (PPIs), called auto-p2docking. Containerized Docker, auto-p2docking ensures reproducibility and reduces number errors through its simplified configuration. Its architecture consists 22 modules, used develop 12 protocols but be specified according user needs. In this work, 45 putative ataxin-3 interactors (53% novel), using interacting regions validation. Furthermore, predict from both Parkin-independent -dependent mechanisms affected polyQ expansion.

Language: Английский

The pro-fibrotic role of autophagy in renal intrinsic cells: mechanisms and therapeutic potential in chronic kidney disease

Frontiers in Cell and Developmental Biology, Journal Year: 2024, Volume and Issue: 12

Published: Dec. 11, 2024

Chronic kidney disease (CKD) represents a significant global public health burden, affecting over 10% of the world’s population. Its high morbidity, multifactorial complications, and substantial mortality impose burdens on healthcare systems patients, necessitating considerable investment in resources. Renal fibrosis (RF) is key pathological feature driver CKD progression. Extensive research indicates that autophagy participates complete pathogenesis RF. Under physiological conditions, essential for maintaining renal cellular homeostasis. However, under perhaps aberrant sustained activation contributes to oxidative stress, apoptosis, inflammation, etc. Ultimately, they accelerate development The role RF currently controversial. This review investigates molecular mechanisms by which intrinsic cell across diverse models, suggesting its associated regulatory pathways represent potential diagnostic therapeutic targets CKD.

Language: Английский