A Perspective on the Development of c-Jun N-terminal Kinase Inhibitors as Therapeutics for Alzheimer's Disease: Investigating Structure through Docking Studies

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초록

c-Jun N-terminal kinase (JNK) plays an important role in cell death caused by various stimuli. Because the isoform JNK3 is mainly expressed in the brain, it is believed to play a pivotal role in various neurodegenerative diseases, including Alzheimer's disease (AD) and Parkinson's disease (PD), which still lack plausible therapeutics. To develop a novel and selective JNK3 inhibitor, we conducted a decadal review (2011 to 2021) of published articles on JNK inhibitors, particularly those focusing on a structural perspective and docking insights. We observed the structures of three isoforms of JNK, namely holo-proteins and co-crystal structures, with JNK3 inhibitors and summarized the significant structural aspects of selective JNK3 inhibitors as AD therapeutics.

키워드

Alzheimer's disease; c-Jun N-terminal kinase; small-molecule protein kinase inhibitor; JNK3; selectivity; CRYSTAL-STRUCTURE; PROTEIN-KINASE; JNK INHIBITOR; OPTIMIZATION; ACTIVATION; DISCOVERY; DESIGN; POTENT; PHOSPHORYLATION; SELECTIVITY
제목
A Perspective on the Development of c-Jun N-terminal Kinase Inhibitors as Therapeutics for Alzheimer's Disease: Investigating Structure through Docking Studies
저자
Cho, Hyunwook; Hah, Jung-Mi
DOI
10.3390/biomedicines9101431
발행일
2021-10
유형
Review
저널명
BIOMEDICINES
권
9
호
10