Autoimmune diseases (ADs) are conditions in which the immune system cannot distinguish self from non-self and, as a result, tissue injury occurs primarily due to the action of various inflammatory mediators. Different immunosuppressive agents are used for the treatment of patients with ADs, but some clinical cases develop resistance to currently available therapies. The proteasome inhibitor bortezomib (BTZ) is an approved agent for first-line therapy of people with multiple myeloma. BTZ has been shown to improve the symptoms of different ADs in animal models and ameliorated symptoms in patients with systemic lupus erythematous, rheumatoid arthritis, myasthenia gravis, neuromyelitis optica spectrum disorder, Chronic inflammatory demyelinating polyneuropathy, and autoimmune hematologic diseases that were nonresponsive to conventional therapies. Proteasome inhibition provides a potent strategy for treating ADs. BTZ represents a proteasome inhibitor that can potentially be used to treat AD patients resistant to conventional therapies.

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10787-021-00863-2DOI Listing

Publication Analysis

Top Keywords

proteasome inhibitor
12
autoimmune diseases
8
therapies proteasome
8
conventional therapies
8
bortezomib proteasome
4
inhibitor treatment
4
treatment autoimmune
4
diseases autoimmune
4
ads
4
diseases ads
4

Similar Publications

Discovery of a potent PROTAC degrader for RNA demethylase FTO as antileukemic therapy.

Acta Pharm Sin B

December 2024

School of Pharmaceutical Science and Technology, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou 310024, China.

The fat mass and obesity-associated protein (FTO) is an RNA demethylase required for catalytic demethylation of -methyladenosine (mA); it is highly expressed and functions as an oncogene in acute myeloid leukemia (AML). Currently, the overarching objective of targeting FTO is to precisely inhibit the catalytic activity. Meanwhile, whether FTO degradation also exerts antileukemic effects remains unknown.

View Article and Find Full Text PDF

Background: Targeting exportin1 (XPO1) with Selinexor (SEL) is a promising therapeutic strategy for patients with multiple myeloma (MM). However, intrinsic and acquired drug resistance constitute great challenges. SEL has been reported to promote the degradation of XPO1 protein in tumor cells.

View Article and Find Full Text PDF

Biosynthesis of lactacystin as a proteasome inhibitor.

Commun Chem

January 2025

Graduate School of Engineering, Hokkaido University, N13-W8, Kita-ku, Sapporo, Hokkaido, 060-8628, Japan.

Lactacystin is an irreversible proteasome inhibitor isolated from Streptomyces lactacystinicus. Despite its importance for its biological activity, the biosynthesis of lactacystin remains unknown. In this study, we identified the lactacystin biosynthetic gene cluster by gene disruption and heterologous expression experiments.

View Article and Find Full Text PDF

NMDAR antagonists, such as memantine and ketamine, have shown efficacy in treating neurodegenerative diseases and major depression. The mechanism by which these drugs correct the aforementioned diseases is still unknown. Our study reveals that these antagonists significantly enhance 20S proteasome activity, crucial for degrading intrinsically disordered, oxidatively damaged, or misfolded proteins, factors pivotal in neurodegenerative diseases like Alzheimer's and Parkinson's.

View Article and Find Full Text PDF

Introduction: Hypoxia, a condition characterized by inadequate oxygen supply to tissues, triggers various cellular responses, including apoptosis. The RNA demethylase FTO has been shown to exert anti-apoptotic effects, but its functions independent of RNA demethylase-particularly those involving protein-protein interactions-during hypoxia remain unclear.

Objectives: This study aimed to elucidate the cytoprotective mechanism of FTO in preventing apoptosis under hypoxic stress.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!