The IQ-1S JNK (c-Jun N-Terminal Kinase) Inhibitor Suppresses Premature Aging of OXYS Rat Brain

Abstract

—According to the Alzheimer’s Disease International (ADI) international organization about 50 million people in the world suffer from Alzheimer’s disease (AD). However, there are no effective methods for preventing or slowing the progression of AD. Inhibition of the c-Jun N-terminal kinase (JNK) signaling pathway is discussed below as an alternative way to prevent the development of AD and other neurodegenerative diseases. In the present study, we evaluated the ability of a recently synthesized selective JNK3 inhibitor, 11H-indeno[1,2-b]quinoxalin-11-one oxime sodium salt (IQ-1S), to suppress neurodegenerative processes in OXYS rats at an early stage of development of AD at the ages of 4.5 to 6 months. Treatment with IQ-1S (50 mg/kg intragastrically) led to the suppression of the development of neurodegenerative processes in the cerebral cortex of OXYS rats: an increase in the proportion of unchanged neurons, a decrease in the proportion of neurons with signs of destruction and irreversible damage, and a normalization of the glioneuronal index, which was facilitated by a decrease in the severity of hyperviscosity syndrome blood in OXYS rats. The use of the IQ-1S JNK3 inhibitor may be a promising strategy for the prevention of early neurodegenerative disorders and, possibly, the treatment of AD.