A Glycosylated Prodrug to Attenuate Neuroinflammation and Improve Cognitive Deficits in Alzheimer's Disease Transgenic Mice

Mingeun Kim; Min Hee Park; Geewoo Nam; Misun Lee; Juhye Kang; Im Sook Song; Min Koo Choi; Hee Kyung Jin; Jae Sung Bae; Mi Hee Lim

doi:10.1021/acs.molpharmaceut.0c00677

A Glycosylated Prodrug to Attenuate Neuroinflammation and Improve Cognitive Deficits in Alzheimer's Disease Transgenic Mice

Mingeun Kim
, Min Hee Park
, Geewoo Nam
, Misun Lee
, Juhye Kang
, Im Sook Song
, Min Koo Choi
, Hee Kyung Jin
, Jae Sung Bae
, Mi Hee Lim

Korea Advanced Institute of Science and Technology
Kyungpook National University
Ulsan National Institute of Science and Technology
Pohang University of Science and Technology
Dankook University

Research output: Contribution to journal › Article › peer-review

11 Scopus citations

Abstract

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.

Original language	English
Pages (from-to)	101-112
Number of pages	12
Journal	Molecular Pharmaceutics
Volume	18
Issue number	1
DOIs	https://doi.org/10.1021/acs.molpharmaceut.0c00677
State	Published - 4 Jan 2021

Keywords

Alzheimer's disease
amyloid-β
anti-neuroinflammation
microglial function
prodrug

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10.1021/acs.molpharmaceut.0c00677

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title = "A Glycosylated Prodrug to Attenuate Neuroinflammation and Improve Cognitive Deficits in Alzheimer's Disease Transgenic Mice",

abstract = "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.",

keywords = "Alzheimer's disease, amyloid-β, anti-neuroinflammation, microglial function, prodrug",

author = "Mingeun Kim and Park, \{Min Hee\} and Geewoo Nam and Misun Lee and Juhye Kang and Song, \{Im Sook\} and Choi, \{Min Koo\} and Jin, \{Hee Kyung\} and Bae, \{Jae Sung\} and Lim, \{Mi Hee\}",

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doi = "10.1021/acs.molpharmaceut.0c00677",

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T1 - A Glycosylated Prodrug to Attenuate Neuroinflammation and Improve Cognitive Deficits in Alzheimer's Disease Transgenic Mice

AU - Kim, Mingeun

AU - Park, Min Hee

AU - Nam, Geewoo

AU - Lee, Misun

AU - Kang, Juhye

AU - Song, Im Sook

AU - Choi, Min Koo

AU - Jin, Hee Kyung

AU - Bae, Jae Sung

AU - Lim, Mi Hee

PY - 2021/1/4

Y1 - 2021/1/4

N2 - 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.

AB - 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.

KW - Alzheimer's disease

KW - amyloid-β

KW - anti-neuroinflammation

KW - microglial function

KW - prodrug

UR - https://www.scopus.com/pages/publications/85097750576

U2 - 10.1021/acs.molpharmaceut.0c00677

DO - 10.1021/acs.molpharmaceut.0c00677

M3 - Article

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AN - SCOPUS:85097750576

SN - 1543-8384

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JO - Molecular Pharmaceutics

JF - Molecular Pharmaceutics

IS - 1

ER -

A Glycosylated Prodrug to Attenuate Neuroinflammation and Improve Cognitive Deficits in Alzheimer's Disease Transgenic Mice

Abstract

Keywords

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