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Can I read Chemical Knockdown of Phosphorylated p38 Mitogen-Activated Protein Kinase (MAPK) as a Novel Approach for the Treatment of Alzheimer′s Disease on EtoBox?
Chemical Knockdown of Phosphorylated p38 Mitogen-Activated Protein Kinase (MAPK) as a Novel Approach for the Treatment of Alzheimer′s Disease by Seung Hwan Son; Na-Rae Lee; Min Sung Gee; Chae Won Song; Soo Jin Lee; Sang-Kyung Lee; Yoonji Lee; Hee Jin Kim; Jong Kil Lee; Kyung-Soo Inn; Nam-Jung Kim is a Biochemistry, Genetics and Molecular Biology article available to read on EtoBox.
What is Chemical Knockdown of Phosphorylated p38 Mitogen-Activated Protein Kinase (MAPK) as a Novel Approach for the Treatment of Alzheimer′s Disease about?
Targeted protein degradation (TPD) provides unique advantages over gene knockdown in that it can induce selective degradation of disease-associated proteins attributed to pathological mutations or aberrant post-translational modifications (PTMs). Herein, we report a protein degrader, PRZ-18002, that selectively binds to an active form of p38 MAPK. PRZ-18002 induces degradation of phosphorylated p38 MAPK (p-p38) and a phosphomimetic mutant of p38 MAPK in a proteasome-dependent manner. Given that the activation of p38 MAPK plays pivotal roles in the pathophysiology of Alzheimer’s disease (AD), selective degradation of p-p38 may provide an attractive therapeutic option for the treatment of AD. In the 5xFAD transgenic mice model of AD, intranasal treatment of PRZ-18002 reduces p-p38 levels and alleviates microglia activation and amyloid beta (Aβ) deposition, leading to subsequent improvement of spatial learning and memory. Collectively, our findings suggest that PRZ-18002 ameliorates AD pathophysiology via selective degradation of p-p38, highlighting a novel therapeutic TPD modality that targets a specific PTM to induce selective degradation of neurodegenerative disease-associated prot
Who reads Chemical Knockdown of Phosphorylated p38 Mitogen-Activated Protein Kinase (MAPK) as a Novel Approach for the Treatment of Alzheimer′s Disease?
It is typically read by researchers, students, and practitioners in Biochemistry, Genetics and Molecular Biology.
- Author
- Seung Hwan Son; Na-Rae Lee; Min Sung Gee; Chae Won Song; Soo Jin Lee; Sang-Kyung Lee; Yoonji Lee; Hee Jin Kim; Jong Kil Lee; Kyung-Soo Inn; Nam-Jung Kim
- Publisher
- American Chemical Society (ACS)
- Published
- 2023
- Language
- EN
- Field
- Biochemistry, Genetics and Molecular Biology (Physical Sciences)