BAP31 deficiency contributes to the formation of amyloid‐β plaques in Alzheimer's disease by reducing the stability of RTN3

Wang, Tianyi; Chen, Jing; Hou, Yue; Yu, Yang; Wang, Bing

doi:10.1096/fj.201801702r

Cited by 21 publications

(13 citation statements)

References 38 publications

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“…The formation of RTN3 aggregates was found to be regulated by B-cell receptor-associated protein 31 (BAP31), an integral ER membrane protein. Silencing of this gene leads to formation of RTN3 aggregates, thereby reducing the interaction with BACE1 which promotes Aβ formation (He et al 2004 ; Wang et al 2019 ). Our functional enrichment analysis revealed the interactions of RTN3 with synaptic proteins and gene expression analysis demonstrated downregulation of this gene.…”

Section: Discussionmentioning

confidence: 99%

Revelation of Pivotal Genes Pertinent to Alzheimer’s Pathogenesis: A Methodical Evaluation of 32 GEO Datasets

2021

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Alzheimer’s disease (AD), a dreadful neurodegenerative disorder that affects cognitive and behavioral function in geriatric populations, is characterized by the presence of amyloid deposits and neurofibrillary tangles in brain regions. The International D World Alzheimer Report 2018 noted a global prevalence of 50 million AD cases and forecasted a threefold rise to 139 million by 2050. Although there exist numerous genetic association studies pertinent to AD in different ethnicities, critical genetic factors and signaling pathways underlying its pathogenesis remain ambiguous. This study was aimed to analyze the genetic data retrieved from 32 Gene Expression Omnibus datasets belonging to diverse ethnic cohorts in order to identify overlapping differentially expressed genes (DEGs). Stringent selection criteria were framed to shortlist appropriate datasets based on false discovery rate (FDR) p -value and log FC, and relevant details of upregulated and downregulated DEGs were retrieved. Among the 32 datasets, only six satisfied the selection criteria. The GEO2R tool was employed to retrieve significant DEGs. Nine common DEGs, i.e., SLC5A3 , BDNF , SST , SERPINA3 , RTN3 , RGS4 , NPTX , ENC1 and CRYM were found in more than 60% of the selected datasets. These DEGs were later subjected to protein–protein interaction analysis with 18 AD-specific literature-derived genes. Among the nine common DEGs, BDNF , SST , SERPINA3 , RTN3 and RGS4 exhibited significant interactions with crucial proteins including BACE1, GRIN2B, APP, APOE, COMT, PSEN1, INS, NEP and MAPT. Functional enrichment analysis revealed involvement of these genes in trans-synaptic signaling, chemical transmission, PI3K pathway signaling, receptor–ligand activity and G protein signaling. These processes are interlinked with AD pathways.

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Section: Discussionmentioning

confidence: 99%

Revelation of Pivotal Genes Pertinent to Alzheimer’s Pathogenesis: A Methodical Evaluation of 32 GEO Datasets

2021

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“…It participates in transporting member proteins from the ER to other organelles, mediating apoptosis via p20 and regulating the ERAD pathway (Breckenridge et al, 2003;Wakana et al, 2008). Our recent study indicates that Bap31 deficiency leads to the formation of amyloid-β plaques via reducing RTN3 stability in Alzheimer's disease (Wang et al, 2019). The conditional knockout of BAP31 in hepatocyte promotes SREBP1C activation and hepatic lipid accumulation and worsens insulin resistance in HFD-induced obesity in mice (Xu et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

B-Cell Receptor-Associated Protein 31 Negatively Regulates the Expression of Monoamine Oxidase A Via R1

Jia

Jiang

et al. 2020

Front. Mol. Biosci.

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B-cell receptor-associated protein 31 (Bap31) is a three trans-membrane protein of the endoplasmic reticulum (ER). Patients who have loss of function of Bap31 suffered from X-linked syndrome, such as motor and intellectual disabilities, dystonia, and sensorineural deafness. However, the underlying mechanism of Bap31 on X-linked syndrome remains unclear. Here, we found that a total of 21 proteins (9 up-regulated and 12 down-regulated proteins) related with X-linked syndrome were screened from shRNA-Bap31 transfected cells with the isobaric tags for relative and absolute quantification (iTRAQ) technique. One gene with the greatest change trend, monoamine oxidase A (MAOA), was identified. MAOA expression was up-regulated by Bap31 knockdown. However, Bap31 did not affect the ubiquitination degradation of MAOA protein. Of note, Bap31 selectively regulated the expression of cell division cycle associated 7-like (R1/RAM2/CDCA7L/JPO2, a transcriptional repressor of MAOA) and the binding activity of R1 with MAOA promoter, thereby affecting MAOA expression. This study demonstrates the molecular mechanisms of Bap31 in MAOA via R1 and supports the potential function of Bap31 on X-linked syndrome.

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“…Bap31, encoded by BCAP31 which we found downregulated, have several roles in ER homeostasis: membrane protein chaperone, quality control, and it is involved in ER stress and ERAD [ 56 ]. Its deficiency was associated with the formation of Aβ plaques in a murine AD model [ 57 ]. P97, encoded by VCP , also plays a critical role in protein dislocation in ERAD [ 46 ]; it is involved in aggregates clearance, and, indeed, its knockdown delayed the elimination of ubiquitin-positive aggregates [ 58 ].…”

Section: Discussionmentioning

confidence: 99%

Δ8-THC Protects against Amyloid Beta Toxicity Modulating ER Stress In Vitro: A Transcriptomic Analysis

Blando

Salamone

Caprioglio

et al. 2023

IJMS

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Alzheimer’s disease (AD) represents the most common form of dementia, characterized by amyloid β (Aβ) plaques and neurofibrillary tangles (NFTs). It is characterized by neuroinflammation, the accumulation of misfolded protein, ER stress and neuronal apoptosis. It is of main importance to find new therapeutic strategies because AD prevalence is increasing worldwide. Cannabinoids are arising as promising neuroprotective phytocompounds. In this study, we evaluated the neuroprotective potential of Δ8-THC pretreatment in an in vitro model of AD through transcriptomic analysis. We found that Δ8-THC pretreatment restored the loss of cell viability in retinoic acid-differentiated neuroblastoma SH-SY5Y cells treated with Aβ1-42. Moreover, the transcriptomic analysis provided evidence that the enriched biological processes of gene ontology were related to ER functions and proteostasis. In particular, Aβ1-42 upregulated genes involved in ER stress and unfolded protein response, leading to apoptosis as demonstrated by the increase in Bax and the decrease in Bcl-2 both at gene and protein expression levels. Moreover, genes involved in protein folding and degradation were also deregulated. On the contrary, Δ8-THC pretreatment reduced ER stress and, as a consequence, neuronal apoptosis. Then, the results demonstrated that Δ8-THC might represent a new neuroprotective agent in AD.

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BAP31 deficiency contributes to the formation of amyloid‐β plaques in Alzheimer's disease by reducing the stability of RTN3

Cited by 21 publications

References 38 publications

Revelation of Pivotal Genes Pertinent to Alzheimer’s Pathogenesis: A Methodical Evaluation of 32 GEO Datasets

Revelation of Pivotal Genes Pertinent to Alzheimer’s Pathogenesis: A Methodical Evaluation of 32 GEO Datasets

B-Cell Receptor-Associated Protein 31 Negatively Regulates the Expression of Monoamine Oxidase A Via R1

Δ8-THC Protects against Amyloid Beta Toxicity Modulating ER Stress In Vitro: A Transcriptomic Analysis

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