C-Jun N-Terminal Kinase Inhibitors As Potential Leads for New Therapeutics for Alzheimer's Diseases

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2020 Dec 23

PMID 33352989

Citations 20

Authors

Stephanie Cristine Hepp Rehfeldt

Fernanda Majolo

Marcia Ines Goettert

Stefan Laufer

Affiliations

Soon will be listed here.

Abstract

Alzheimer's Disease (AD) is becoming more prevalent as the population lives longer. For individuals over 60 years of age, the prevalence of AD is estimated at 40.19% across the world. Regarding the cognitive decline caused by the disease, mitogen-activated protein kinases (MAPK) pathways such as the c-Jun N-terminal kinase (JNK) pathway are involved in the progressive loss of neurons and synapses, brain atrophy, and augmentation of the brain ventricles, being activated by synaptic dysfunction, oxidative stress, and excitotoxicity. Nowadays, AD symptoms are manageable, but the disease itself remains incurable, thus the inhibition of JNK3 has been explored as a possible therapeutic target, considering that JNK is best known for its involvement in propagating pro-apoptotic signals. This review aims to present biological aspects of JNK, focusing on JNK3 and how it relates to AD. It was also explored the recent development of inhibitors that could be used in AD treatment since several drugs/compounds in phase III clinical trials failed. General aspects of the MAPK family, therapeutic targets, and experimental treatment in models are described and discussed throughout this review.

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