A Glycosylated Prodrug to Attenuate Neuroinflammation and Improve Cognitive Deficits in Alzheimer’s Disease Transgenic Mice,Molecular Pharmaceutics

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A Glycosylated Prodrug to Attenuate Neuroinflammation and Improve Cognitive Deficits in Alzheimer’s Disease Transgenic Mice
Molecular Pharmaceutics ( IF 4.5 ) Pub Date : 2020-11-26 , DOI: 10.1021/acs.molpharmaceut.0c00677
Mingeun Kim ₁ , Min Hee Park _{2,

3,

4} , Geewoo Nam ₁ , Misun Lee ₅ , Juhye Kang _{1,

6} , Im-Sook Song ₇ , Min-Koo Choi ₈ , Hee Kyung Jin _{2,

9} , Jae-Sung Bae _{2,

3,

4} , Mi Hee Lim ₁

Affiliation

Department of Chemistry, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea.
KNU Alzheimer's disease Research Institute, Kyungpook National University, Daegu 41566, Republic of Korea.
Department of Physiology, School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea.
Department of Biomedical Science, BK21 Plus Kyungpook National University Biomedical Convergence Program, Kyungpook National University, Daegu 41944, Republic of Korea.
Department of Chemistry, Ulsan National Institute of Science and Technology (UNIST), Ulsan 44919, Republic of Korea.
Technical Support Center, Office of Research Affairs, Pohang University of Science and Technology, Pohang 37673, Republic of Korea.
College of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 41566, Republic of Korea.
College of Pharmacy, Dankook University, Cheon-an 31116, Republic of Korea.
Department of Laboratory Animal Medicine, College of Veterinary Medicine, Kyungpook National University, Daegu 41566, Republic of Korea.

We report a prodrug, Glu-DAPPD, to overcome the shortcomings of an anti-neuroinflammatory molecule, N,N′-diacetyl-p-phenylenediamine (DAPPD), in biological applicability for potential therapeutic applications. We suspect that Glu-DAPPD can release DAPPD through endogenous enzymatic bioconversion. Consequently, Glu-DAPPD exhibits in vivo efficacies in alleviating neuroinflammation, reducing amyloid-β aggregate accumulation, and improving cognitive function in Alzheimer’s disease transgenic mice. Our studies demonstrate that the prodrug approach is suitable and effective toward developing drug candidates against neurodegeneration.

中文翻译：

一种用于减轻阿尔茨海默病转基因小鼠神经炎症和改善认知缺陷的糖基化前药

我们报告了一种前药Glu-DAPPD，以克服抗神经炎症分子N,N'-二乙酰-对苯二胺 ( DAPPD ) 在潜在治疗应用的生物学适用性方面的缺点。我们怀疑Glu-DAPPD可以通过内源性酶促生物转化释放DAPPD。因此，Glu-DAPPD在减轻神经炎症、减少淀粉样蛋白 β 聚集体积累和改善阿尔茨海默病转基因小鼠的认知功能方面表现出体内功效。我们的研究表明，前药方法适用于开发针对神经变性的候选药物。

更新日期：2021-01-04

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