Peroxisome Proliferator-Activated Receptor-Gamma (PPAR-ɣ): Molecular Effects and Its Importance as a Novel Therapeutic Target for Cerebral Ischemic Injury

• Published in: Neurochemical research Vol. 46; no. 11; pp. 2800 - 2831
• Main Authors: Mannan, Ashi, Garg, Nikhil, Singh, Thakur Gurjeet, Kang, Harmeet Kaur
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.11.2021; Springer Nature B.V
• Subjects: Angiogenesis; Animals; Antitumor activity; Apoptosis; Biochemistry; Biomedical and Life Sciences; Biomedicine; Brain - drug effects; Brain - metabolism; Brain injury; Brain Ischemia - drug therapy; Brain Ischemia - metabolism; Cell Biology; Deoxyribonucleic acid; DNA; Drug Delivery Systems - methods; Drug Delivery Systems - trends; Gene expression; Humans; Inflammation; Injuries; Insulin; Ischemia; Ligands; Lipid metabolism; Lipids; Literature reviews; Modulation; Molecular modelling; Neurochemistry; Neurogenesis; Neurology; Neurons - drug effects; Neurons - metabolism; Neuroprotection; Neuroprotective Agents - administration & dosage; Neurosciences; Oxidative stress; Peroxisome proliferator-activated receptors; PPAR gamma - agonists; PPAR gamma - metabolism; Receptors; Regulatory sequences; Review; Therapeutic targets; Transcription factors; Peroxisome proliferator activated receptor gamma; Angiogenesis; Neuroinflammation; Insulin; Neurogenesis; Cerebral ischemic injury
• ISSN: 0364-3190; 1573-6903
• DOI: 10.1007/s11064-021-03402-1

Cerebral ischemic injury is a leading cause of death and long-term disability throughout the world. Peroxisome proliferator-activated receptor gamma (PPAR-ɣ) is a ligand-activated nuclear transcription factor that is a member of the PPAR family. PPAR-ɣ has been shown in several in vitro and in vivo models to prevent post-ischemic inflammation and neuronal damage by negatively controlling the expression of genes modulated by cerebral ischemic injury, indicating a neuroprotective effect during cerebral ischemic injury. A extensive literature review of PubMed, Medline, Bentham, Scopus, and EMBASE (Elsevier) databases was carried out to understand the nature of the extensive work done on the mechanistic role of Peroxisome proliferator activated receptor gamma and its modulation in Cerebral ischemic injury. PPAR-ɣ can interact with specific DNA response elements to control gene transcription and expression when triggered by its ligand. It regulates lipid metabolism, improves insulin sensitivity, modulates antitumor mechanisms, reduces oxidative stress, and inhibits inflammation. This review article provides insights on the current state of research into the neuroprotective effects of PPAR-ɣ in cerebral ischemic injury, as well as the cellular and molecular mechanisms by which these effects are modulated, such as inhibition of inflammation, reduction of oxidative stress, suppression of pro-apoptotic production, modulation of transcription factors, and restoration of injured tissue through neurogenesis and angiogenesis.