TARGETING ALZHEIMER’S DISEASE WITH CARNOSIC ACID: THERAPEUTIC MODULATION OF THE P2X7 RECEPTOR–NLRP3 INFLAMMASOME PATHWAY IN RAT MODELS

Abstract

Alzheimer disease is a progressive neurodegenerative disorder which illustrates cognitive loss, synaptic dysfunction and neuronal loss. There are emerging accumulating evidences that chronic neuroinflammation is at the center of the pathogenesis of the disease as well as traditional amyloid beta and tau pathology. The purinergic P2X7 receptor and NLRP3 inflammasome signalling are two of the main types of inflammatory mechanism induction to be found to be controlling the activation of microglia and long-term maintenance of inflammatory signals in the brain with Alzheimer disease. Carnosic acid is a natural phenolic diterpene compound which is mainly produced by rosemary and has received interest due to its strong antioxidant behavior as well as anti-inflammatory effects. In preclinical studies of rat models of Alzheimer disease, carnosic acid positively affects cognitive behavior, neuroinflammatory reactions, oxidative stress, and P2X7 receptor-mediated NLRP3 inflammasome activation. Carnosic acid is a multi-target therapeutic agent by blocking upstream stress and downstream inflammatory pathways. The article is a review that summarizes what is known today as to the role of P2X7 receptor and NLRP3 inflammasome in the pathogenesis of Alzheimer disease and critically assesses whether carnosic acid can act as neuroprotective in preclinical rat models. Mechanistic understandings, comparative study to other treatment therapies, difficulties in clinical translation and future research perspectives are also presented. Altogether, carnosic acid is a potentially valid candidate to include in inflammation-based therapeutic approaches in the case of Alzheimer disease.