Title:Kinase Inhibitors Involved in the Regulation of Autophagy: Molecular
Concepts and Clinical Implications
Volume: 30
Issue: 13
Author(s): Isehaq Al-Huseini, Srinivasa Rao Sirasanagandla, Kondaveeti Suresh Babu, Ramakrishna Gopala Sumesh Sofin and Srijit Das*
Affiliation:
- Department of Human and Clinical Anatomy, College of Medicine and Health Sciences,
Sultan Qaboos University, Muscat, Al-Khodh 123, Oman
Keywords:
Autophagy, signaling pathways, kinase inhibitors, drug delivery, cellular degradation, molecular concepts.
Abstract: All cells and intracellular components are remodeled and recycled in order to
replace the old and damaged cells. Autophagy is a process by which damaged, and unwanted
cells are degraded in the lysosomes. There are three different types of autophagy:
macroautophagy, microautophagy, and chaperone-mediated autophagy. Autophagy has
an effect on adaptive and innate immunity, suppression of any tumour, and the elimination
of various microbial pathogens. The process of autophagy has both positive and negative
effects, and this pertains to any specific disease or its stage of progression. Autophagy
involves various processes which are controlled by various signaling pathways, such
as Jun N-terminal kinase, GSK3, ERK1, Leucine-rich repeat kinase 2, and PTEN-induced
putative kinase 1 and parkin RBR E3. Protein kinases are also important for the
regulation of autophagy as they regulate the process of autophagy either by activation or
inhibition. The present review discusses the kinase catalyzed phosphorylated reactions,
the kinase inhibitors, types of protein kinase inhibitors and their binding properties to protein
kinase domains, the structures of active and inactive kinases, and the hydrophobic
spine structures in active and inactive protein kinase domains. The intervention of autophagy
by targeting specific kinases may form the mainstay of treatment of many diseases
and lead the road to future drug discovery.