ORP150‐CHIP chaperone antagonism control BACE1‐mediated amyloid processing

Chanana, Neha; Pati, Uttam

doi:10.1002/jcb.26630

Cited by 3 publications

(3 citation statements)

References 52 publications

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“…36 HYOU1 can protect neurons from cell death and plays an important role in neurodegenerative diseases. 25,[37][38][39] HYOU1 can protect cardiomyocytes and vascular cells from apoptosis, and plays an important role in improving atherosclerosis and regulating cardiac ischemia/reperfusion.…”

Section: Structure and Function Of Hyou1mentioning

confidence: 99%

“…HYOU1 signaling plays an essential role in neurodegenerative diseases. 25,[37][38][39] The common symptom of many neurodegenerative diseases is the accumulation of misfolded proteins in the lumen of nerve cells, especially Alzheimer's disease and Parkinson's disease. 62 The study found that in post-mortem brain tissues and cell culture models, upregulation of ER stress markers was observed in diseases such as Alzheimer's disease and Parkinson's disease.…”

Section: Role Of Hyou1 In Neurodegenerative Diseasesmentioning

confidence: 99%

“…68 Studies had found that Aβ42 in Alzheimer's disease can be prevented by inhibiting HYOU1 or activating the E3-ligase activity of CHIP. 37 Over-expression of HYOU1 under stress can protect neurons from cell death. The data indicate that endoplasmic reticulum stress may be the main cause of neuronal cell death, and HYOU1 may become a promising neuroprotective mediator.…”

Section: Role Of Hyou1 In Neurodegenerative Diseasesmentioning

confidence: 99%

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Biological Function of HYOU1 in Tumors and Other Diseases

Rao¹,

Oyang²,

Liang³

et al. 2021

OTT

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Various stimuli induce an unfolded protein response to endoplasmic reticulum stress, accompanied by the expression of endoplasmic reticulum molecular chaperones. Hypoxia-upregulated 1 gene (HYOU1) is a chaperone protein located in the endoplasmic reticulum. HYOU1 expression was upregulated in many diseases, including various cancers and endoplasmic reticulum stress-related diseases. HYOU1 does not only play an important protective role in the occurrence and development of tumors, but also is a potential therapeutic target for cancer. HYOU1 may also be used as an immune stimulation adjuvant because of its anti-tumor immune response, and a molecular target for therapy of many endoplasmic reticulum-related diseases. In this article, we summarize the updates in HYOU1 and discuss the potential therapeutic effects of HYOU1.

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Section: Structure and Function Of Hyou1mentioning

confidence: 99%

Section: Role Of Hyou1 In Neurodegenerative Diseasesmentioning

confidence: 99%

Section: Role Of Hyou1 In Neurodegenerative Diseasesmentioning

confidence: 99%

See 1 more Smart Citation

Biological Function of HYOU1 in Tumors and Other Diseases

Rao¹,

Oyang²,

Liang³

et al. 2021

OTT

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Chemical Regulation of the Protein Quality Control E3 Ubiquitin Ligase C‐Terminus of Hsc70 Interacting Protein (CHIP)

et al. 2022

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The ubiquitin ligase C-terminus of Hsc70 interacting protein (CHIP) is an important regulator of proteostasis. Despite playing an important role in maintaining proteostasis, little progress has been made in developing small molecules that regulate ubiquitin transfer by CHIP. Here we used differential scanning fluorimetry to identify compounds that bound CHIP. Compounds that bound CHIP were then analyzed by quantitative ubiquitination assays to identify those that altered CHIP function. One compound, MS.001, inhibited both the chaperone binding and ubiquitin ligase activity of CHIP at low micromolar concentrations. Interestingly, we found that MS.001 did not have activity against isolated U-box or tetratricopeptide (TPR) domains, but instead only inhibited full-length CHIP. Using in silico docking we identified a potential MS.001 binding site on the linker domain of CHIP and mutation of this site rendered CHIP resistant to MS.001. Together our data identify an inhibitor of the E3 ligase CHIP and provides insight into the development of compounds that regulate CHIP activity.

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AAV mediated carboxyl terminus of Hsp70 interacting protein overexpression mitigates the cognitive and pathological phenotypes of APP/PS1 mice

Hu,

Yang,

Zhang

et al. 2024

Neural Regeneration Research

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JOURNAL/nrgr/04.03/01300535-202501000-00033/figure1/v/2024-05-14T021156Z/r/image-tiff The E3 ubiquitin ligase, carboxyl terminus of heat shock protein 70 (Hsp70) interacting protein (CHIP), also functions as a co-chaperone and plays a crucial role in the protein quality control system. In this study, we aimed to investigate the neuroprotective effect of overexpressed CHIP on Alzheimer’s disease. We used an adeno-associated virus vector that can cross the blood-brain barrier to mediate CHIP overexpression in APP/PS1 mouse brain. CHIP overexpression significantly ameliorated the performance of APP/PS1 mice in the Morris water maze and nest building tests, reduced amyloid-β plaques, and decreased the expression of both amyloid-β and phosphorylated tau. CHIP also alleviated the concentration of microglia and astrocytes around plaques. In APP/PS1 mice of a younger age, CHIP overexpression promoted an increase in ADAM10 expression and inhibited β-site APP cleaving enzyme 1, insulin degrading enzyme, and neprilysin expression. Levels of HSP70 and HSP40, which have functional relevance to CHIP, were also increased. Single nuclei transcriptome sequencing in the hippocampus of CHIP overexpressed mice showed that the lysosomal pathway and oligodendrocyte-related biological processes were up-regulated, which may also reflect a potential mechanism for the neuroprotective effect of CHIP. Our research shows that CHIP effectively reduces the behavior and pathological manifestations of APP/PS1 mice. Indeed, overexpression of CHIP could be a beneficial approach for the treatment of Alzheimer’s disease.

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ORP150‐CHIP chaperone antagonism control BACE1‐mediated amyloid processing

Cited by 3 publications

References 52 publications

Biological Function of HYOU1 in Tumors and Other Diseases

Biological Function of HYOU1 in Tumors and Other Diseases

Chemical Regulation of the Protein Quality Control E3 Ubiquitin Ligase C‐Terminus of Hsc70 Interacting Protein (CHIP)

AAV mediated carboxyl terminus of Hsp70 interacting protein overexpression mitigates the cognitive and pathological phenotypes of APP/PS1 mice

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