The role of genetic risk factors of Alzheimer's disease in synaptic dysfunction

Fu, Wing‐Yu; Ip, Nancy Y.

doi:10.1016/j.semcdb.2022.07.011

Cited by 22 publications

(12 citation statements)

References 117 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Alzheimer’s disease (AD) is the prevalent type of dementia in the elderly population. AD is characterized by memory loss and deterioration of other cognitive functions including comprehension, judgment, and orientation due to synaptic loss and selective neuronal death [ 46 ]. AD brains are characterized by the accumulation of extracellular senile plaques composed of deposits of β-amyloid peptides Aβ (1–40) and Aβ (1–42), as well as intracellular neurofibrillary tangles (NFTs) composed of aggregates of the hyperphosphorylated tau protein [ 40 ].…”

Section: Implication Of Oxidative Stress and Nrf2 Activation In Neuro...mentioning

confidence: 99%

Activators of Nrf2 to Counteract Neurodegenerative Diseases

2023

View full text Add to dashboard Cite

Neurodegenerative diseases are incurable and debilitating conditions that result in progressive degeneration and loss of nerve cells. Oxidative stress has been proposed as one factor that plays a potential role in the pathogenesis of neurodegenerative disorders since neuron cells are particularly vulnerable to oxidative damage. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is strictly related to anti-inflammatory and antioxidative cell response; therefore, its activation and the consequent enhancement of the related cellular pathways have been proposed as a potential therapeutic approach. Several Nrf2 activators with different mechanisms and diverse structures have been reported, but those applied for neurodisorders are still limited. However, in the very last few years, interesting progress has been made, particularly in enhancing the blood–brain barrier penetration, to make Nrf2 activators effective drugs, and in designing Nrf2-based multitarget-directed ligands to affect multiple pathways involved in the pathology of neurodegenerative diseases. The present review gives an overview of the most representative findings in this research area.

show abstract

Section: Implication Of Oxidative Stress and Nrf2 Activation In Neuro...mentioning

confidence: 99%

Activators of Nrf2 to Counteract Neurodegenerative Diseases

2023

View full text Add to dashboard Cite

show abstract

“…A variety of immune cells were signi cantly in ltrated in Cluster 2, and multiple biological processes related to synapse formation were signi cantly upregulated in Cluster 2. M2 macrophages have signi cant anti-in ammatory properties and can improve cognitive dysfunction in AD model mice [24], and increased synapse formation is associated with improved cognitive function [25]. Based on this, we speculate that the AD process of Cluster 2 patients may be suppressed, resulting in a better prognosis.…”

Section: Discussionmentioning

confidence: 78%

Identification of pyroptosis-related molecular clusters in alzheimer’s disease based on multiple machine learning models

Fan

Niu

Wang

et al. 2023

Preprint

View full text Add to dashboard Cite

Background: Alzheimer's disease (AD) is the most common neurodegenerative disease. Pyroptosis is a new type of programmed cell death, which can lead to the progression of various diseases. The aim of this study was to explore the role of pyroptosis-related genes (PRGs) in Alzheimer's disease and to build the predictive model. Methods: The expression of PRGs in AD was analyzed based on the GSE33000 dataset, and molecular clustering and immune microenvironment analysis were performed on 310 patient samples. The WGCNA algorithm was used to identify the genes that were specifically expressed between different clusters, and then four machine learning models (RF, GLM, SVM and XGB) were used to construct the predictive models for the risk of AD. The prediction capability of the model was verified by nomogram, calibration, decision curve analyses and five external data sets. Results: Multiple PRGs were differentially expressed between AD and normal brain tissue. Based on differentially expressed PRGs, 310 AD patients were divided into two subtypes by consistent clustering. Immune microenvironment analysis showed significant differences in the degree of immune activation among different subtypes. WGCNA algorithm identified the specific genes between AD and normal individuals, Cluster 1 and Cluster 2. The SVM model has the best prediction performance with low residual error and root mean square error, and high area under ROC curve (AUC=0.933). Finally, a prediction model based on five genes (GPR4, STAT3, CASP4, CLIC1 and TNFRSF10B) was constructed and showed satisfactory performance on five externally validated data sets. Nomogram, calibration curve and decision curve analysis proved the prediction performance of the model. Conclusions: This study systematically analyzed the complex relationship between PRGs and AD, and constructed a good prediction model to distinguish AD from normal individuals, which is expected to provide reference for related research.

show abstract

“…The interaction of numerous genes involved in neuronal plasticity in the determinism or protection from dementia is also very complex ( 14 ). The paradigm of molecular biology is that the function of proteins is determined by genes encoding for them.…”

Section: Dementia Heterogeneity Genes Proteins the Exposome And The “...mentioning

confidence: 99%