4.7 Review

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

Journal

BIOMEDICINES
Volume 9, Issue 10, Pages -

Publisher

MDPI
DOI: 10.3390/biomedicines9101431

Keywords

Alzheimer's disease; c-Jun N-terminal kinase; small-molecule protein kinase inhibitor; JNK3; selectivity

Funding

  1. National Research Foundation of Korea [NRF-2020R1A6A1A03042854, NRF-2021R1A2C2007159]

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JNK3 plays a crucial role in neurodegenerative diseases, and this study summarizes the research on JNK3 inhibitors, focusing on structural and docking insights.
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.

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