Ethnopharmacological Relevant: Dendrobium is a traditional and precious Chinese medicinal herb. The Compendium of Materia Medica describes its effects as "benefiting intelligence and dispelling shock, lightning the body and extending life". Dendrobium nobile Lindl. is a precious variety of Dendrobium. Our previous data showed Dendrobium nobile Lindl. alkaloid (DNLA) has significant neuroprotective effects and can improve cognitive dysfunction. However, the specific effects and mechanisms of action of its main active component, DNLA, on cognitive dysfunction caused by Tau hyperphosphorylation, are still unclear.
Aim Of The Research: This study aimed to determine the effects of DNLA on phosphatidylinositol-3 kinase (PI3K)/protein kinase B (Akt)/glycogen synthase kinase 3β (GSK-3β) pathway, thus to explore the mechanisms of DNLA to inhibit Tau hyperphosphorylation.
Materials And Methods: We used wortmannin (WM) and GF-109203X (GFX)-induced hyperphosphorylation of Tau in N2a cells and rats to detect the protective mechanism of DNLA in vivo and in vitro. In vitro, the effect of modeling method on Tau hyperphosphorylation was screened and verified by Western Blotting (WB), and the regulation of Tau hyperphosphorylation and PI3K/Akt/GSK-3β pathway by different concentrations of DNLA was detected by WB. In vivo, MWM was used to detect the effect of DNLA on model rats, and then Nissl staining was used to detect the loss of neurons. Finally, WB was used to detect the regulation of Tau hyperphosphorylation and PI3K/Akt/GSK-3β pathway by different concentrations of DNLA.
Results: DNLA could rescue the abnormal PI3K/Akt/GSK-3β pathway and reverse the hyperphosphorylation of Tau induced by WM and GFX in N2a cells. Furthermore, DNLA improved the learning and memory of WM and GFX-induced model rats. Moreover, DNLA regulated PI3K/Akt/GSK-3β pathway and reduced the p-Tau and neuronal damage in the hippocampus of model rats.
Conclusion: DNLA may be a promising candidate for reducing hyperphosphorylation of Tau.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.jep.2023.117592 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Age-related p53 SUMOylation accelerates senescence and tau pathology in Alzheimer's disease.
Cell Death Differ
January 2025
Department of Pathophysiology, School of Basic Medicine, Key Laboratory of Education Ministry/Hubei Province of China for Neurological Disorders, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Aging is a major risk factor for Alzheimer's disease (AD). With the prevalence of AD increased, a mechanistic linkage between aging and the pathogenesis of AD needs to be further addressed. Here, we report that a small ubiquitin-related modifier (SUMO) modification of p53 is implicated in the process which remarkably increased in AD patient's brain.
View Article and Find Full Text PDFDesign, Current States, and Challenges of Nanomaterials in Anti-Neuroinflammation: A Perspective on Alzheimer's Disease.
Ageing Res Rev
January 2025
Department of Alzheimer's Disease Clinical Research Center, Guangdong Second Provincial General Hospital, Guangzhou, 510317, China; Jinan University, Guangzhou,510000, China; School of Basic Medical Sciences, Shenzhen University, Shenzhen,518060, China. Electronic address:
Alzheimer's disease (AD), an age-related neurodegenerative disease, brings huge damage to the society, to the whole family and even to the patient himself. However, until now, the etiological factor of AD is still unknown and there is no effective treatment for it. Massive deposition of amyloid-beta peptide(Aβ) and hyperphosphorylation of Tau proteins are acknowledged pathological features of AD.
View Article and Find Full Text PDFEvaluating amyloid-beta aggregation and toxicity in transgenic Caenorhabditis elegans models of Alzheimer's disease.
Methods Cell Biol
January 2025
Federal University of Santa Maria, Center for Natural and Exact Sciences, Department of Biochemistry and Molecular Biology, Graduate Program in Biological Sciences: Toxicological Biochemistry, Camobi, Santa Maria, RS, Brazil.
Alzheimer's disease (AD) is the leading cause of dementia in the elderly, clinically characterized by memory loss, cognitive decline, and behavioral disturbances. Its pathogenesis is not fully comprehended but involves intracellular depositions of amyloid beta peptide (Aβ) and neurofibrillary tangles of hyperphosphorylated tau. Currently, pharmacological interventions solely slow the progression of symptoms.
View Article and Find Full Text PDFThe current models unravel the molecular mechanisms underlying the intricate pathophysiology of Alzheimer's disease using zebrafish.
Methods Cell Biol
January 2025
Department of Pharmacology, SPP School of Pharmacy & Technology Management, Mumbai, India. Electronic address:
The foremost cause of dementia is Alzheimer's disease (AD). The vital pathological hallmarks of AD are amyloid beta (Aβ) peptide and hyperphosphorylated tau (p-tau) protein. The current animal models used in AD research do not precisely replicate disease pathophysiology, making it difficult for researchers to quickly and effectively gather data or screen potential therapy possibilities.
View Article and Find Full Text PDFHyperphosphorylated Tau and Cognition in Epilepsy.
J Clin Med
January 2025
Department of Epileptology, University Hospital Bonn (UKB), 53127 Bonn, Germany.
In light of the growing interest in the bidirectional relationship between epilepsy and dementia, this review aims to provide an overview of the role of hyperphosphorylated tau (pTau) in cognition in human epilepsy. A literature search identified five relevant studies. All of them examined pTau burden in surgical biopsy specimens from patients with temporal lobe epilepsy.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!