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

Hyunwook Cho; Jung-Mi Hah

doi:10.3390/biomedicines9101431

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

Biomedicines. 2021 Oct 9;9(10):1431. doi: 10.3390/biomedicines9101431.

Authors

Hyunwook Cho^{1

2}, Jung-Mi Hah^{1

2}

Affiliations

¹ Department of Pharmacy, College of Pharmacy, Hanyang University, Ansan 15588, Korea.
² Center for Proteinopathy, Institute of Pharmaceutical Science and Technology, Hanyang University, Ansan 15588, Korea.

Abstract

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.

Keywords: Alzheimer’s disease; JNK3; c-Jun N-terminal kinase; selectivity; small-molecule protein kinase inhibitor.

Publication types

Review

Abstract

Publication types

Grants and funding