The Mechanistic Role of Bridging Integrator 1 (BIN1) in Alzheimer’s Disease

Gao, Peirong; Ye, Lingqi; Cheng, Hong-Rong; Li, Honglei

doi:10.1007/s10571-020-00926-y

Cited by 21 publications

(23 citation statements)

References 92 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We also observed a genome-wide (GW) significant (p < 5×10 -8 ) association of BIN1 (rs4663105, MAF=0.47, OR=1.17, p=3.2×10 -9 ) with AD status in the pooled samples analysis. Previous studies have identified BIN1 as an AD susceptibility gene after APOE 12,14,25 . After adjusting for APOE ⍰4 (rs429358) and ⍰2 (rs7412) alleles on chromosome 19, the association of BIN1 on chromosome 2 remained largely the same (OR=1.17, p=3.1×10 -9 ).…”

Section: Resultsmentioning

confidence: 99%

Association of Common and Rare Variants with Alzheimer’s Disease in over 13,000 Diverse Individuals with Whole-Genome Sequencing from the Alzheimer’s Disease Sequencing Project

Lee,

Choi,

Shea

et al. 2023

Preprint

View full text Add to dashboard Cite

Alzheimer’s Disease (AD) is a common disorder of the elderly that is both highly heritable and genetically heterogeneous. Here, we investigated the association between AD and both common variants and aggregates of rare coding and noncoding variants in 13,371 individuals of diverse ancestry with whole genome sequence (WGS) data. Pooled-population analyses identified genetic variants in or nearAPOE, BIN1, andLINC00320significantly associated with AD (p < 5×10-8). Population-specific analyses identified a haplotype on chromosome 14 includingPSEN1associated with AD in Hispanics, further supported by aggregate testing of rare coding and noncoding variants in this region. Finally, we observed suggestive associations (p < 5×10-5) of aggregates of rare coding rare variants inABCA7among non-Hispanic Whites (p=5.4×10-6), and rare noncoding variants in the promoter ofTOMM40distinct ofAPOEin pooled-population analyses (p=7.2×10-8). Complementary pooled-population and population-specific analyses offered unique insights into the genetic architecture of AD.

show abstract

Section: Resultsmentioning

confidence: 99%

Association of Common and Rare Variants with Alzheimer’s Disease in over 13,000 Diverse Individuals with Whole-Genome Sequencing from the Alzheimer’s Disease Sequencing Project

Lee,

Choi,

Shea

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…BIN1 plays a role in cell cycle control and can mediate cell apoptosis via a caspase‐independent process (Elliott et al., 2000; Galderisi et al., 1999) but mechanistic details are unclear. Also unclear is whether BIN1‐related apoptosis is involved in AD (Gao et al., 2021). Future studies should explore these two proteins in AD in greater detail, together with NQO1.…”

Section: Discussionmentioning

confidence: 99%

NQO1 regulates expression and alternative splicing of apoptotic genes associated with Alzheimer's disease in PC12 cells

Liu

Chen³

et al. 2023

Brain and Behavior

View full text Add to dashboard Cite

Purpose: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive memory loss and cognitive dysfunction. Quinone oxidoreductase 1 (NQO1) is an antioxidant enzyme that plays an important role in controlling cellular redox state, whose expression is altered in the brain tissues of AD patients. In addition to its traditional antioxidant effects, NQO1 also acts as a multifunctional RNA-binding protein involved in posttranscriptional regulation. Whether the RNA-binding activity of NQO1 influences AD pathology has not been investigated yet. Methods:The RNA-binding functions of NQO1 in rat pheochromocytoma (PC12) cells were investigated using siRNA knockdown followed by total RNA sequencing. Reverse transcription quantitative polymerase chain reaction was performed to explore the impact of NQO1 on the transcription and alternative splicing of apoptotic genes.Results: NQO1 knockdown led to a significant increase in cellular apoptosis. Genes involved in certain apoptosis pathways, such as positive regulation of apoptotic processes and mitogen-activated protein kinase signaling, were under global transcriptional and alternative splicing regulation. NQO1 regulated the transcription of apoptotic genes Cryab, Lgmn, Ngf, Apoe, Brd7, and Stat3, as well as the alternative splicing of apoptotic genes BIN1, Picalm, and Fyn. Conclusion:Our findings suggest that NQO1 participates in the pathology of AD by regulating the expression and alternative splicing of the genes involved in apoptosis. These results extend our understanding of NQO1 in apoptotic pathways at the posttranscriptional level in AD.

show abstract

“…(1) Concerning the filter parameters (IMPACT is HIGH or IMPACT is MODERATE and SIFT <0.05 and BIOTYPE is protein_coding) of the pipeline, SNPs located in non-coding regions of relevant genes (e.g., APP [40]) are excluded. Moreover, more famous and consolidated susceptibility genes (e.g., APOE [41], BIN1 [42], TNK1 [43] and so on.) seem to be filtered out, possibly due to the lower cohort of AD data in ADNI.…”

Section: Discussionmentioning

confidence: 99%

Annotating whole genome variants and constructing a multi-classifier based on samples of ADNI

Zhou¹,

Qiu²,

Liu³

et al. 2022

Front. Biosci. (Landmark Ed)

View full text Add to dashboard Cite

Introduction: Alzheimer's disease (AD) is the most common progressive neurodegenerative disorder in the elderly, which will eventually lead to dementia without an effective precaution and treatment. As a typical complex disease, the mechanism of AD's occurrence and development still lacks sufficient understanding. Research design and methods: In this study, we aim to directly analyze the relationship between DNA variants and phenotypes based on the whole genome sequencing data. Firstly, to enhance the biological meanings of our study, we annotate the deleterious variants and mapped them to nearest protein coding genes. Then, to eliminate the redundant features and reduce the burden of downstream analysis, a multi-objective evaluation strategy based on entropy theory is applied for ranking all candidate genes. Finally, we use multi-classifier XGBoost for classifying unbalanced data composed with 46 AD samples, 483 mild cognitive impairment (MCI) samples and 279 cognitive normal (CN) samples. Results: The experimental results on real whole genome sequencing data from Alzheimer's Disease Neuroimaging Initiative (ADNI) show that our method not only has satisfactory classification performance but also finds significance correlation between AD and RIN3, a known susceptibility gene of AD. In addition, pathway enrichment analysis was carried out using the top 20 feature genes, and three pathways were confirmed to be significantly related to the formation of AD. Conclusions: From the experimental results, we demonstrated that the efficacy of our proposed method has practical significance.

show abstract

The Mechanistic Role of Bridging Integrator 1 (BIN1) in Alzheimer’s Disease

Cited by 21 publications

References 92 publications

Association of Common and Rare Variants with Alzheimer’s Disease in over 13,000 Diverse Individuals with Whole-Genome Sequencing from the Alzheimer’s Disease Sequencing Project

Association of Common and Rare Variants with Alzheimer’s Disease in over 13,000 Diverse Individuals with Whole-Genome Sequencing from the Alzheimer’s Disease Sequencing Project

NQO1 regulates expression and alternative splicing of apoptotic genes associated with Alzheimer's disease in PC12 cells

Annotating whole genome variants and constructing a multi-classifier based on samples of ADNI

Contact Info

Product

Resources

About