A Combination Therapy of Urolithin A+EGCG Has Stronger Protective Effects than Single Drug Urolithin A in a Humanized Amyloid Beta Knockin Mice for Late-Onset Alzheimer’s Disease DOI Creative Commons
Sudhir Kshirsagar,

Rainier Vladlen Alvir,

Jangampalli Adi Pradeepkiran

et al.

Cells, Journal Year: 2022, Volume and Issue: 11(17), P. 2660 - 2660

Published: Aug. 27, 2022

In the current study, for first time, we study mitophagy enhancer urolithin A and a combination of A+green tea extract EGCG against human Aβ peptide-induced mitochondrial synaptic, dendritic, inflammatory toxicities behavioral changes in humanized homozygous amyloid beta knockin (hAbKI) mice late-onset Alzheimer's disease (AD). Our findings reveal significantly increased positive effects treatment A+EGCG hAbKI phenotypic including motor coordination, locomotion/exploratory activity, spatial learning working memory. mRNA protein levels fusion, autophagy genes were upregulated, fission are downregulated combine mice; however, effect is stronger combined treatment. Immunofluorescence analysis hippocampal brain sections shows similar levels. Mitochondrial dysfunction reduced both groups, but reduction observed Dendritic spines lengths The fragmented number mitochondria reduced, length increased, mitophagosomal formations (Aβ) 40 Aβ42 treatments, higher These observations suggest that protective toxicities; effective stronger, indicating therapy promising to treat AD patients.

Language: Английский

The role of mitochondrial quality surveillance in skin aging: Focus on mitochondrial dynamics, biogenesis and mitophagy DOI
Chang Zhang, Xingyu Gao,

Minghe Li

et al.

Ageing Research Reviews, Journal Year: 2023, Volume and Issue: 87, P. 101917 - 101917

Published: March 25, 2023

Language: Английский

Citations

36
Targeting dynamin-related protein-1 as a potential therapeutic approach for mitochondrial dysfunction in Alzheimer's disease DOI Creative Commons
Jasvinder Singh Bhatti, Satinder Kaur, Jayapriya Mishra

et al.

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Journal Year: 2023, Volume and Issue: 1869(7), P. 166798 - 166798

Published: June 29, 2023

Language: Английский

Citations

36
An Approach toward Artificial Intelligence Alzheimer’s Disease Diagnosis Using Brain Signals DOI Creative Commons
Seyed‐Ali Sadegh‐Zadeh, Elham Fakhri, Mahboobe Bahrami

et al.

Diagnostics, Journal Year: 2023, Volume and Issue: 13(3), P. 477 - 477

Published: Jan. 28, 2023

Background: Electroencephalography (EEG) signal analysis is a rapid, low-cost, and practical method for diagnosing the early stages of dementia, including mild cognitive impairment (MCI) Alzheimer’s disease (AD). The extraction appropriate biomarkers to assess subject’s has attracted lot attention in recent years. aberrant progression AD leads cortical detachment. Due interaction several brain areas, these disconnections may show up as abnormalities functional connectivity complicated behaviors. Methods: This work suggests novel differentiating between AD, MCI, HC two-class three-class classifications based on EEG signals. To solve class imbalance, we employ data augmentation techniques, such repeating minority classes using variational autoencoders (VAEs), well traditional noise-addition methods hybrid approaches. power spectrum density (PSD) temporal employed this study’s feature from signals were combined, support vector machine (SVM) classifier was used distinguish three categories problems. Results: Insufficient unbalanced datasets are two common problems datasets. study shown that it possible generate comparable noise addition VAE, train model data, and, some extent, overcome aforementioned issues with an increase classification accuracy 2 7%. Conclusion: In work, able successfully detect classes: HC. comparison pre-augmentation stage, gained increased by 3% when VAE added additional data. As result, clear how useful smaller sample numbers.

Language: Английский

Citations

30
Mitochondria in Aging and Alzheimer’s Disease: Focus on Mitophagy DOI
Jangampalli Adi Pradeepkiran,

Javaria Baig,

Ann Seman

et al.

The Neuroscientist, Journal Year: 2023, Volume and Issue: 30(4), P. 440 - 457

Published: Jan. 3, 2023

Alzheimer’s disease (AD) is characterized by the accumulation of amyloid β and phosphorylated τ protein aggregates in brain, which leads to loss neurons. Under microscope, function mitochondria uniquely primed play a pivotal role neuronal cell survival, energy metabolism, death. Research studies indicate that mitochondrial dysfunction, excessive oxidative damage, defective mitophagy neurons are early indicators AD. This review article summarizes latest development AD: 1) mechanism pathways, 2) importance functions, 3) metabolic pathways 4) link between dysfunction mechanisms AD, 5) potential mitochondrial-targeted therapeutics interventions treat patients with

Language: Английский

Citations

29
Damaged mitochondria coincide with presynaptic vesicle loss and abnormalities in alzheimer’s disease brain DOI Creative Commons
Wenzhang Wang, Fanpeng Zhao, Yubing Lu

et al.

Acta Neuropathologica Communications, Journal Year: 2023, Volume and Issue: 11(1)

Published: March 31, 2023

Abstract Loss of synapses is the most robust pathological correlate Alzheimer’s disease (AD)-associated cognitive deficits, although underlying mechanism remains incompletely understood. Synaptic terminals have abundant mitochondria which play an indispensable role in synaptic function through ATP provision and calcium buffering. Mitochondrial dysfunction early prominent feature AD could contribute to deficits. Here, using electron microscopy, we examined with a focus on mitochondrial deficits presynaptic axonal dendritic spines cortical biopsy samples from clinically diagnosed age-matched non-AD control patients. vesicle density within axon was significantly decreased cases appeared largely due reserve pool, but there were more axons containing enlarged vesicles or dense core AD. Importantly, reduced number along increased damaged presynapse correlated changes SV density. Mitochondria post-synaptic also samples. This study provided evidence loss as suggested that both pre- compartments

Language: Английский

Citations

26
Evaluation and targeting of amyloid precursor protein (APP)/amyloid beta (Aβ) axis in amyloidogenic and non-amyloidogenic pathways: A time outside the tunnel DOI
Hayder M. Al‐kuraishy, Majid S. Jabir, Ali I. Al‐Gareeb

et al.

Ageing Research Reviews, Journal Year: 2023, Volume and Issue: 92, P. 102119 - 102119

Published: Nov. 4, 2023

Language: Английский

Citations

25
CKLF induces microglial activation via triggering defective mitophagy and mitochondrial dysfunction DOI
Hongyun Wang,

Jun-rui Ye,

Ye Peng

et al.

Autophagy, Journal Year: 2023, Volume and Issue: 20(3), P. 590 - 613

Published: Nov. 1, 2023

Although microglial activation is induced by an increase in chemokines, the role of mitophagy this process remains unclear. This study aimed to elucidate CKLF/CKLF1 (chemokine-like factor 1)-induced and neuroinflammation, as well underlying molecular mechanisms following CKLF treatment. determined that CKLF, inducible chemokine brain, leads markers, such DNM1L, PINK1 (PTEN putative kinase 1), PRKN, OPTN, along with a simultaneous autophagosome formation, evidenced elevated levels BECN1 MAP1LC3B (microtubule-associated protein 1 light chain 3 beta)-II. However, SQSTM1, substrate autophagy, was also accumulated treatment, suggesting flux reduced mitophagosomes accumulated. These findings were confirmed transmission electron microscopy confocal microscopy. The defective observed our caused impaired lysosomal function, including mitophagosome-lysosome fusion, lysosome generation, acidification, resulting accumulation damaged mitochondria cells. Further analysis revealed pharmacological blocking or gene-silencing inhibited CKLF-mediated activation, expression marker AIF1 (allograft inflammatory 1) mRNA proinflammatory cytokines (Tnf Il6). Ultimately, results brains adult mice. In summary, induces mitophagy, inflammation, providing potential approach for treating neuroinflammatory diseases.

Language: Английский

Citations

23
Exploring Advancements in Early Detection of Alzheimer's Disease with Molecular Assays and Animal Models DOI
Papihra Sethi, Rakesh Bhaskar, Krishna Kumar Singh

et al.

Ageing Research Reviews, Journal Year: 2024, Volume and Issue: 100, P. 102411 - 102411

Published: July 9, 2024

Language: Английский

Citations

15
Genetic and multi‐omic risk assessment of Alzheimer's disease implicates core associated biological domains DOI Creative Commons
Gregory A. Cary, Jesse C. Wiley, Jake Gockley

et al.

Alzheimer s & Dementia Translational Research & Clinical Interventions, Journal Year: 2024, Volume and Issue: 10(2)

Published: April 1, 2024

Abstract INTRODUCTION Alzheimer's disease (AD) is the predominant dementia globally, with heterogeneous presentation and penetrance of clinical symptoms, variable presence mixed pathologies, potential subtypes, numerous associated endophenotypes. Beyond difficulty designing treatments that address core pathological characteristics disease, therapeutic development challenged by uncertainty which endophenotypic areas specific targets implicated those endophenotypes to prioritize for further translational research. However, publicly funded consortia driving large‐scale open science efforts have produced multiple omic analyses both risk relevance biological process involvement genes across genome. METHODS Here we report an informatic pipeline draws from genetic association studies, predicted variant impact, linkage phenotypes create a score. This paired multi‐omic score utilizing extensive sets transcriptomic proteomic studies identify system‐level changes in expression AD. These two elements combined constitute our target ranks AD genome‐wide. The ranked are organized into space through 19 domains described genetics genomics accompanying literature. constructed exhaustive Gene Ontology (GO) term compilations, allowing automated assignment objectively defined disease‐associated biology. rank‐and‐organize approach, performed genome‐wide, allows characterization aggregations domains. RESULTS top AD‐risk‐associated Synapse, Immune Response, Lipid Metabolism, Mitochondrial Structural Stabilization, Proteostasis, slightly lower levels enrichment present within other 13 DISCUSSION provides objective methodology localize drill down most significantly GO terms annotated targets.

Language: Английский

Citations

12
Mitochondrial dynamics and mitochondrial autophagy: Molecular structure, orchestrating mechanism and related disorders DOI Creative Commons
Haoran Wang,

Wenjun Luo,

Haoyu Chen

et al.

Mitochondrion, Journal Year: 2024, Volume and Issue: 75, P. 101847 - 101847

Published: Jan. 19, 2024

Mitochondrial dynamics and autophagy play essential roles in normal cellular physiological activities, while abnormal mitochondrial can cause cancer related disorders. Abnormal usually occur parallel with autophagy. Both have been reported to a synergistic effect therefore complement or inhibit each other. Progress has made understanding the classical PINK1/Parkin pathway dynamical abnormalities. Still, mechanisms regulatory pathways underlying interaction between mitophagy remain unexplored. Like other existing reviews, we review molecular structure of proteins involved autophagy, how their abnormalities lead development diseases. We will also individual effects leading proliferation, differentiation invasion. In addition, explore contribute targeted precise regulation function. Through study mechanisms, as well role early disease development, effective targets for function be proposed enable accurate diagnosis treatment associated

Language: Английский

Citations

11