Mechanistic exploration of ubiquitination-mediated pathways in cerebral ischemic injury DOI

Supriya Khanra,

Shareen Singh,

Thakur Gurjeet Singh

et al.

Molecular Biology Reports, Journal Year: 2024, Volume and Issue: 52(1)

Published: Nov. 28, 2024

Language: Английский

Deubiquitination of RIPK3 by OTUB2 potentiates neuronal necroptosis after ischemic stroke DOI Creative Commons

Fuqi Mei,

Dongrui Deng,

Zi-Jun Cao

et al.

EMBO Molecular Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 28, 2025

Abstract As a common and severe cerebrovascular disease, ischemic stroke casts significant shadow over global health. Unfortunately, the mechanisms regulating neuronal death in affected areas remain largely unclear. Here, we found that deletion of deubiquitinating enzyme Otubain-2 (OTUB2) significantly alleviated ischemia-induced cerebral infarction neurological deficits, accompanied by reduction loss, glial activation, neuroinflammation. OTUB2 was predominantly expressed neurons its decreased receptor-interacting protein kinase 3 (RIPK3)-mediated necroptosis. Moreover, increased RIPK3 abundance inhibiting proteasomal degradation RIPK3. Mechanistically, removed K48-linked polyubiquitin chains from through active site C51. Importantly, pharmacological inhibition brain injury mice reduced oxygen-glucose deprivation-induced human organoids. These results demonstrate critically regulates potentiating necroptosis, suggesting may become potential therapeutic approach for treating stroke.

Language: Английский

Citations

1
Ubiquitous regulation of cerebrovascular diseases by ubiquitin‐modifying enzymes DOI Creative Commons
Jingyong Huang,

Zhenhu Zhu,

Dirk Schlüter

et al.

Clinical and Translational Medicine, Journal Year: 2024, Volume and Issue: 14(5)

Published: May 1, 2024

Abstract Cerebrovascular diseases (CVDs) are a major threat to global health. Elucidation of the molecular mechanisms underlying pathology CVDs is critical for development efficacious preventative and therapeutic approaches. Accumulating studies have highlighted significance ubiquitin‐modifying enzymes (UMEs) in regulation CVDs. UMEs group that orchestrate ubiquitination, post‐translational modification tightly involved Functionally, regulate multiple pathological processes ischemic hemorrhagic stroke, moyamoya disease, atherosclerosis. Considering important roles CVDs, they may become novel druggable targets these diseases. Besides, techniques applying UMEs, such as proteolysis‐targeting chimera deubiquitinase‐targeting chimera, also revolutionize therapy future.

Language: Английский

Citations

7
A cross-tissue transcriptome-wide association study identifies new key genes in ischemic stroke DOI

Zhiwei Song,

Yupeng Han,

Wangyu Li

et al.

Gene, Journal Year: 2025, Volume and Issue: unknown, P. 149207 - 149207

Published: Jan. 1, 2025

Language: Английский

Citations

0
DUBA sustains the stability of NOD2 and RIPK2 to enhance innate immune responses DOI

Bincheng Zhou,

Mengsha Yin, Xian Su

et al.

Cell Death and Differentiation, Journal Year: 2025, Volume and Issue: unknown

Published: April 16, 2025

Language: Английский

Citations

0
Novel Isoxazolidines Derivatives as RIPK1 Inhibitors for Treating Neurodegenerative Diseases DOI
Ram W. Sabnis

ACS Medicinal Chemistry Letters, Journal Year: 2025, Volume and Issue: 16(5), P. 754 - 755

Published: April 17, 2025

Provided herein are novel isoxazolidines derivatives as RIPK1 inhibitors, pharmaceutical compositions, use of such compounds in treating neurodegenerative diseases, and processes for preparing compounds.

Language: Английский

Citations

0
Ubiquitin: Not just a one‐way ticket to the proteasome, but a therapeutic dial to fine‐tune the molecular landscape of disease DOI Creative Commons
Albert H. Kim,

Peter M. Chiknas,

Robin Lee

et al.

Clinical and Translational Medicine, Journal Year: 2024, Volume and Issue: 14(7)

Published: July 1, 2024

Abstract Recently, there is a rise in studies that recognize the importance of targeting ubiquitin and related molecular machinery various therapeutic contexts. Here we briefly discuss history ubiquitin, its biological roles protein degradation beyond, as well current state ubiquitin‐targeting therapeutics across diseases. We conclude approaching renaissance, tapping full potential will require embracing wholistic perspective ubiquitin's multifaceted roles.

Language: Английский

Citations

3
Mechanistic exploration of ubiquitination-mediated pathways in cerebral ischemic injury DOI

Supriya Khanra,

Shareen Singh,

Thakur Gurjeet Singh

et al.

Molecular Biology Reports, Journal Year: 2024, Volume and Issue: 52(1)

Published: Nov. 28, 2024

Language: Английский

Citations

2