Τίτλος:
Synthetic and Natural Inhibitors of Phospholipases A2: Their Importance for Understanding and Treatment of Neurological Disorders
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Phospholipases A2 (PLA2) are a diverse group of enzymes that hydrolyze membrane phospholipids into arachidonic acid and lysophospholipids. Arachidonic acid is metabolized to eicosanoids (prostaglandins, leukotrienes, thromboxanes), and lysophospholipids are converted to platelet-activating factors. These lipid mediators play critical roles in the initiation, maintenance, and modulation of neuroinflammation and oxidative stress. Neurological disorders including excitotoxicity; traumatic nerve and brain injury; cerebral ischemia; Alzheimers disease; Parkinsons disease; multiple sclerosis; experimental allergic encephalitis; pain; depression; bipolar disorder; schizophrenia; and autism are characterized by oxidative stress, inflammatory reactions, alterations in phospholipid metabolism, accumulation of lipid peroxides, and increased activities of brain phospholipase A2 isoforms. Several old and new synthetic inhibitors of PLA2, including fatty acid trifluoromethyl ketones; methyl arachidonyl fluorophosphonate; bromoenol lactone; indole-based inhibitors; pyrrolidine-based inhibitors; amide inhibitors, 2-oxoamides; 1,3-disubstituted propan-2-ones and polyfluoroalkyl ketones as well as phytochemical based PLA2 inhibitors including curcumin, Ginkgo biloba and Centella asiatica extracts have been discovered and used for the treatment of neurological disorders in cell culture and animal model systems. The purpose of this review is to summarize information on selective and potent synthetic inhibitors of PLA2 as well as several PLA2 inhibitors from plants, for treatment of oxidative stress and neuroinflammation associated with the pathogenesis of neurological disorders. © 2015 American Chemical Society.
Συγγραφείς:
Ong, W.-Y.
Farooqui, T.
Kokotos, G.
Farooqui, A.A.
Περιοδικό:
ACS Chemical Neuroscience
Εκδότης:
American Chemical Society
Λέξεις-κλειδιά:
acetone; amide; bromoenol lactone; fluoroketone derivative; fluorophosphonic acid derivative; indole derivative; natural product; oxoamide derivative; phospholipase A2; phospholipase A2 inhibitor; unclassified drug; phospholipase A2 inhibitor, Alzheimer disease; Article; autism; bipolar disorder; brain injury; brain ischemia; clinical trial (topic); depression; drug potency; excitotoxicity; experimental autoimmune encephalomyelitis; human; multiple sclerosis; nerve degeneration; nervous system inflammation; nervous system injury; neuralgia; neurologic disease; neuropsychiatry; nonhuman; oxidative stress; Parkinson disease; phase 1 clinical trial (topic); phase 2 clinical trial (topic); priority journal; schizophrenia; animal; Brain Diseases; chemistry; enzymology; Mental Disorders; Neurodegenerative Diseases, Animalia; Centella asiatica; Ginkgo biloba, Animals; Brain Diseases; Humans; Mental Disorders; Neurodegenerative Diseases; Phospholipase A2 Inhibitors
DOI:
10.1021/acschemneuro.5b00073
