Pharmacological targeting of molecular machinery of human malarial parasite for development of novel anti malarials

Abstract

Certainly! Here s a concise summary of the abstract: newline newline2-cis, 4-trans-Abscisic Acid (ABA) is an ancient hormone found in cyanobacteria, bridging the gap between plants and animals. In animals, it influences metabolic responses, stimulates skeletal muscles, and regulates energy requirements even at nanomolar concentrations. ABA also impacts blood glucose levels and maintains a healthy body mass index in prediabetic individuals. As a weak acid composed of 15-carbon terpenoids, ABA plays roles in physiology, biotic, and abiotic stress management. newline newlineStudies on marine sponges reveal that ABA production increases under environmental stress, such as changes in light and temperature. ABA triggers responses like enhanced oxygen consumption, water filtration, and regeneration. These effects involve signaling cascades mediated by cAMP, PKA, and cADPR, facilitating calcium export. newline newlineIn mammals, immune cells and tissues release ABA during environmental stress caused by physical or chemical factors. However, exogenous ABA can lead to pro-inflammatory responses, cell migration, reactive oxygen species generation, and phagocytosis. newline newlineRecently, ABA s significance has extended to human red blood cells, where blood ABA levels correlate with malaria severity. Plasma ABA orchestrates malaria parasite egress and invasion by altering calcium homeostasis via NMDAR1. ABA binds to LANCL2, increasing intraerythrocytic cAMP levels, activating Protein Kinase A (PKA), and phosphorylating NMDAR1. Downregulating LANCL2 restricts ABA-dependent calcium signaling, blocking parasite invasion. Pioglitazone, which targets LANCL2, synergizes with artemisinin, reducing parasite load. newline newlineIn summary, Plasma ABA plays a crucial role in host erythrocyte signaling, regulating malaria parasite growth. LANCL2 emerges as a potential druggable target for controlling invasion and egress.