Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
Background: Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by hyperphosphorylation of tau protein to form neurofibrillary tangles (NFTs) and amyloid β (Aβ) deposition to form senile plaques, and its specific regulatory mechanism remains incompletely understood. Neurotrophic factors (NTFs) play important roles in neuronal growth, differentiation, and survival, and are considered to have potential therapeutic effects in AD.
Objective: This study aimed to investigate the effects of NTFs on tau protein phosphorylation in AD and its underlying mechanisms.
Methods: A correlation analysis was conducted between neurotrophic factors and tau protein phosphorylation genes using bioinformatics analysis. The relationship between the candidate neurotrophic factor NRN1 and tau protein phosphorylation was validated . The effects of NRN1 on tau protein phosphorylation, neural process-related proteins, and apoptosis were explored . Subsequently, GO and KEGG pathway enrichment analyses and PPI network were utilized to identify potential functions and pathways, as well as pinpoint core regulatory factors. Finally, the mechanism by which NRN1 affects tau protein phosphorylation was explored through Western blot analysis.
Results: Bioinformatics analysis revealed a significant negative correlation between NRN1 and MAPT, a gene linked to tau protein phosphorylation. Western blot analysis indicated a decrease in NRN1 expression and an increase in p-tau levels in the hippocampus of AD mice. NRN1 significantly reduced the expression of p-tau in AD cell models and enhanced the expression of MAP2, a protein related to neural processes. Further, apoptosis analysis demonstrated that NRN1 significantly decreased the level of cleaved caspase-3 and elevated the Bcl-2/Bax ratio. Bioinformatics analysis and PPI network construction suggested PIGU and CASP3 to play pivotal roles in NRN1 regulation of tau protein phosphorylation.
Conclusion: NRN1 may mitigate tau protein phosphorylation and neuronal apoptosis by modulating the PIGU-CASP3 pathway in AD. This finding offers novel insights into NRN1 as a potential target for the treatment of AD.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.2174/0115672050361366250328040542 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
The study of plaques and tangles makes few and inaccurate predictions about the main features of cognitive disorders: A narrative review.
J Alzheimers Dis
September 2025
IRCCS Fondazione Don Carlo Gnocchi ONLUS, Milan, Italy.
The "biological view" of Alzheimer's disease (AD) focuses on the role of plaques and tangles and excludes syndromes from the disease definition. However, cognitive syndromes are fundamental aspects of AD and are the ultimate target of treatments. Accordingly, the study of cognitive syndromes should remain a major goal of AD research.
View Article and Find Full Text PDFAbnormal Amyloid-β Duration, Tau, and Neurodegeneration in Cranial Images.
JAMA Netw Open
September 2025
School of Medicine and Public Health, University of Wisconsin-Madison, Madison.
Importance: It is unclear whether the duration of amyloid-β (Aβ) pathology is associated with neurodegeneration and whether this depends on the presence of tau.
Objective: To examine the association of longitudinal atrophy with Aβ positron emission tomography (PET)-positivity (Aβ+) and the estimated duration of Aβ+ (Aβ+ duration), controlling for tau-positivity.
Design, Setting, And Participants: Data for this longitudinal cohort study were drawn from the Wisconsin Registry for Alzheimer Prevention and the Wisconsin Alzheimer Disease Research Center Clinical Core Study.
Exploring LRP-1 in the liver-brain axis: implications for Alzheimer's disease.
Mol Biol Rep
September 2025
Department of Pharmacology, Govt. College of Pharmacy, Rohru, Shimla, Himachal Pradesh, 171207, India.
Alzheimer's disease (AD) is the most common, complex, and untreatable form of dementia which is characterized by severe cognitive, motor, neuropsychiatric, and behavioural impairments. These symptoms severely reduce the quality of life for patients and impose a significant burden on caregivers. The existing therapies offer only symptomatic relief without addressing the underlying silent pathological progression.
View Article and Find Full Text PDFCalycosin attenuates neuronal ferroptosis in Alzheimer's disease mice by activating the Nrf2/HO-1 pathway.
Gen Physiol Biophys
September 2025
Department of Neurology, Hubei Third People's Hospital of Jianghan University, Wuhan, China.
In this study, we investigated the therapeutic potential of calycosin (from Astragalus) in Alzheimer's disease (AD), focusing on ferroptosis modulation. APP/PS1 mice received 40 mg/kg calycosin for 3 months. Cognitive function was assessed via Morris water maze test.
View Article and Find Full Text PDFPlasma lipidome dysregulation in frontotemporal dementia reveals shared, genotype-specific, and severity-linked alterations.
Alzheimers Dement
September 2025
Cell Biology Program, Sloan Kettering Institute, New York, New York, USA.
Introduction: Biomarkers are essential for monitoring the progression of frontotemporal dementia (FTD). Although dysregulated brain lipid metabolism, particularly sphingolipids enriched in the nervous system, is a key feature of neurodegeneration, plasma lipids remain underexplored as biomarkers compared to imaging and serum proteins.
Methods: We examined plasma lipidomes using liquid chromatography-tandem mass spectrometry (LC-MS/MS) from individuals carrying pathogenic variants linked to autosomal dominant FTD (GRN, C9orf72, MAPT) and non-carriers.