Polysaccharide from Ganoderma sinense improves cognitive capacity in a mouse model of Alzheimer’s disease via reshaping the gut microbiota and short-chain fatty acid metabolism DOI Creative Commons
Wenjuan Bian, Jiaxuan Wang,

Yudi Jin

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 10, 2024

Abstract Two types of polysaccharides from Ganoderma sinense termed GSP1 (Mw: 58.92 kDa, consisting fourteen monosaccharides) and GSP2 3.27 were purified, their protective effects against Alzheimer's disease (AD) in a mouse model investigated. An vitro study suggested that GSPs protect SH-SY5Y cells neurotoxicity oxidative stress response to glutamate. The effect on the cognitive memory capacity AD was confirmed using Morris Water Maze, Object Recognition, Nestlet Shredding tests. Additionally, treatment with could reduce amyloid β plaques brains mice. Multi-omics analysis gut microbiome, short-chain fatty acid (SCFAs) metabolomics, behavioral tests conducted elucidate therapeutic mechanisms GSPs. results revealed improved diversity restored structure microflora, regulated SCFA metabolism. Four genera (Turicibacter, Jeotgalicoccus, Staphylococcusa, Odoribacter) significantly associated both SCFAs metabolism GSP1-treated group. These findings provide basis for development polysaccharide drugs further GSP1.

Language: Английский

Repurposing of FDA-approved drugs as dual-acting MAO-B and AChE inhibitors against Alzheimer's disease: An in silico and in vitro study DOI Creative Commons
Emilio Mateev, Magdalena Kondeva-Burdina, Maya Georgieva

et al.

Journal of Molecular Graphics and Modelling, Journal Year: 2023, Volume and Issue: 122, P. 108471 - 108471

Published: April 14, 2023

An in silico consensus molecular docking approach and vitro evaluations were adopted the present study to explore a dataset of FDA-approved drugs as novel multitarget MAO-B/AChE agents treatment Alzheimer's disease (AD). GOLD 5.3 Glide employed virtual assessments superimpositions obtained poses applied increase reliability protocols. Furthermore, top ranked molecules subjected binding free energy calculations using MM/GBSA, Induced fit (IFD) simulations, literature review. Consequently, four examined for their MAO-B AChE inhibition effects. The identified Dolutegravir, Rebamipide, Loracarbef Diflunisal potential drugs. biological data demonstrated that most scores good correlation with experiments, however theoretical simulations active site two false-positives – Rebamipide Diflunisal. Dolutegravir accessed inhibitors, while Rebamapide inhibitors. antiretroviral agent exhibited potent activity - 41% (1 μM) 68% (10 μM). Visualizations intermolecular interactions sites revealed formation several stable hydrogen bonds. Overall, was anti-AD drug, further vivo should be considered.

Language: Английский

Citations

13
Lutein, a versatile carotenoid: Insight on neuroprotective potential and recent advances DOI

Megha Jayakanthan,

Janani Manochkumar,

Thomas Efferth

et al.

Phytomedicine, Journal Year: 2024, Volume and Issue: 135, P. 156185 - 156185

Published: Nov. 1, 2024

Language: Английский

Citations

4
Regulation of mitochondrial dysfunction by estrogens and estrogen receptors in Alzheimer's disease: A focused review DOI Creative Commons
Shokouh Arjmand, Mehran Ilaghi,

Ali Karimi Sisakht

et al.

Basic & Clinical Pharmacology & Toxicology, Journal Year: 2024, Volume and Issue: 135(2), P. 115 - 132

Published: May 27, 2024

Alzheimer's disease (AD) is a neurodegenerative disorder that primarily manifests itself by progressive memory loss and cognitive decline, thus significantly affecting functions quality of life. In this review, we proceed from the understanding canonical amyloid-β hypothesis, while significant, has faced setbacks, highlighting need to adopt broader perspective considering intricate interplay diverse pathological pathways for effective AD treatments. Sex differences in offer valuable insights into better its pathophysiology. Fluctuation levels ovarian sex hormones during perimenopause associated with changes glucose metabolism, as possible window opportunity further understand roles steroid their receptors pathophysiology AD. We review these dimensions, emphasizing potential estrogen (ERs) reveal mitochondrial search research therapeutic strategies pharmacotherapy. Understanding addressing interactions dysfunction ERs potentially pave way more approaches therapy.

Language: Английский

Citations

3
Extracellular vesicle and CRISPR gene therapy: Current applications in Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease DOI Creative Commons
Enes Akyüz, Feyza Şule Aslan, Enise Gokce

et al.

European Journal of Neuroscience, Journal Year: 2024, Volume and Issue: 60(8), P. 6057 - 6090

Published: Sept. 19, 2024

Neurodegenerative diseases are characterized by progressive deterioration of the nervous system. Alzheimer's disease (AD), Parkinson's (PD), amyotrophic lateral sclerosis (ALS), and Huntington's (HD) prominently life-threatening examples neurodegenerative diseases. The complexity pathophysiology in causes difficulties diagnosing. Although drugs temporarily help to correct specific symptoms including memory loss degeneration, a complete treatment has not been found yet. New therapeutic approaches have developed understand treat underlying pathogenesis With this purpose, clustered-regularly interspaced short palindromic repeats/CRISPR-associated protein (CRISPR/Cas) technology recently suggested new option. Editing genome is carried out insertion deletion processes on DNA. Safe delivery CRISPR/Cas system targeted cells without affecting surrounding frequently investigated. Extracellular vesicles (EVs), that exosomes, used studies. In review, EV for diagnosis and/or AD, PD, ALS, HD reviewed. technologies, which stand as approaches, may offer definitive option

Language: Английский

Citations

3
Taohong siwu decoction ameliorates cognitive dysfunction through SIRT6/ER stress pathway in Alzheimer's disease DOI

Hong-Yu Tan,

Can Wan,

Guang-Liang Wu

et al.

Journal of Ethnopharmacology, Journal Year: 2023, Volume and Issue: 314, P. 116580 - 116580

Published: May 2, 2023

Language: Английский

Citations

7
GLP-1/Sigma/RAGE receptors: An evolving picture of Alzheimer's disease pathology and treatment DOI

Neha Neha,

Zitin Wali,

Pinky Pinky

et al.

Ageing Research Reviews, Journal Year: 2023, Volume and Issue: 93, P. 102134 - 102134

Published: Nov. 25, 2023

Language: Английский

Citations

7
Decoding Paradoxical Links of Cytokine Markers in Cognition: Cross talk between Physiology, Inflammaging, and Alzheimer’s Disease- Related Cognitive Decline DOI
Hiba Khan,

Talib Naseem,

Pooja Kaushik

et al.

Ageing Research Reviews, Journal Year: 2024, Volume and Issue: 101, P. 102535 - 102535

Published: Oct. 6, 2024

Language: Английский

Citations

2
Advances in the Study of the Pathology and Treatment of Alzheimer’s Disease and Its Association with Periodontitis DOI Creative Commons

Dan Tang,

Chang Sun,

Jumei Yang

et al.

Life, Journal Year: 2023, Volume and Issue: 13(11), P. 2203 - 2203

Published: Nov. 13, 2023

Alzheimer's disease (AD) has become one of the leading causes health problems in elderly, and studying its treatments remains a serious challenge for researchers worldwide. The two main pathological features are extracellular deposition β-amyloid (Aβ) to form senile plaques intracellular aggregation hyperphosphorylated Tau protein neurofibrillary tangles (NFTs). Researchers have proposed several hypotheses elucidate pathogenesis AD, but due complexity pathophysiologic factors involved development no effective drugs been found stop progression disease. Currently, mainstay used treat AD can only alleviate patient's symptoms do not therapeutic effect. As explore interactions among diseases, much evidence suggests that there is close link between periodontitis periodontal pathogenic bacteria exacerbate Aβ hyperphosphorylation through neuroinflammatory mechanisms, thereby advancing AD. This article reviews recent advances available agents, relevance mechanisms action.

Language: Английский

Citations

6
Omaveloxolone ameliorates cognitive dysfunction in APP/PS1 mice by stabilizing the STAT3 pathway DOI Creative Commons
Xiaolin Cui, Shuai Zong,

Wenao Song

et al.

Life Sciences, Journal Year: 2023, Volume and Issue: 335, P. 122261 - 122261

Published: Nov. 10, 2023

To determine the availability and potential molecular mechanisms underlying therapeutic effect of omaveloxolone (RTA408) on Alzheimer's Disease (AD).This study employed network pharmacology to assess feasibility drug treatment AD. cognitive status emotional state APPswe/PS1dE9 (APP/PS1) mice after RTA408 treatment, three classical behavioral experiments (water maze, Y-maze, open field test) were conducted. Immunofluorescence immunohistochemical staining utilized evaluate hippocampal neuronal amyloid (Aβ) deposition in mice. RNA-seq transcription factor prediction analyses performed explore regulating effects RTA408. Molecular docking was predict direct targets. validate these mechanisms, quantitative reverse PCR (qRT-PCR), Western blotting, immunofluorescence two instrumental cell lines, i.e., mouse cells (HT22) microglia (BV2).RTA408 revealed with capability reduce Aβ plaque restore damaged neurons region APP/PS1 mice, ultimately leading an improvement function. This beneficial achieved by balancing STAT3 pathway. Specifically, facilitated activations both STAT3/OXR1 NRF2/ARE axes, thereby enhancing compromised resistance oxidative stress. inhibited NFκB/IL6/STAT3 pathway, effectively countering neuroinflammation triggered microglial activation.RTA408 is promising AD based preclinical data.

Language: Английский

Citations

5
Navigating the Landscape of Alzheimer's Disease: From Epidemiology to Drug Re-purposing DOI Creative Commons

Karishma Rathi,

Ritesh P. Bhole, Prachi Bansode

et al.

Advances in Pharmacology and Pharmacy, Journal Year: 2024, Volume and Issue: 12(2), P. 135 - 148

Published: Feb. 4, 2024

Alzheimer's disease (AD) is a prevalent and complex neurodegenerative disorder, primarily affecting the elderly population characterized by cognitive decline.It diagnosed based on presence of neurotic plaques neurofibrillary tangles in brain.The prevalence AD increasing, existing treatments, such as acetylcholinesterase inhibitors memantine, aim to alleviate symptoms rather than provide cure.These treatments have limitations side effects, leading urgent need for innovative therapies.This review discusses challenges current explores potential future approaches.Precision medicine, epigenetic interventions, immunotherapy, anti-amyloid anti-tau agents, drug repurposing are promising strategies that offer benefits addressing underlying pathology AD.Drug repurposing, particular, highlighted cost-effective time-saving approach accelerating development.Illustrative examples repurposed drugs presented, shedding light this strategy effective treatments.Moreover, involve experimental methods like binding assays phenotypic screening, well computational approaches driven AI.Collaboration among diverse stakeholders use extensive databases enhance efforts.Examples molecules include anti-diabetic certain anti-cancer showing treatment.Thalidomide's anti-inflammatory properties combat AD-related inflammation.PD-1 blockers Pembrolizumab activate immune system against AD.Imatinib shows neuroprotective effects.Antibiotics, antivirals, calcium channel blockers, angiotensin receptor erectile dysfunction therapy.

Language: Английский

Citations

1