Paraoxonase in Nervous System

Abstract

The paraoxonase (PON) family consists of—PON1, PON2 and PON3 which are anti-oxidative, any dysfunction in their action, has been suggested to play a role in the pathobiology of diseases having a chronic inflammatory component. PON1 is the most studied which has paraoxonase, arylesterase, thiolactonase, and anti-oxidant actions. Studies have shown the association between lowered PON1 activity and increased incidence of ischemic stroke, dementia, Parkinson disease, multiple sclerosis, and amyotrophic lateral sclerosis. It may occur due to increased oxidative stress and/or prolonged exposure to organophosphates, and reduced capacity of the body to counter these stresses due to reduced PON1 function. PON2 has arylesterase, lactonase, and antioxidant properties. Under-expression of PON2 is associated with Parkinson Disease and Amyotrophic Lateral Sclerosis, and over-expression with tumors with glioblastoma. Various mechanisms have been proposed for the role of PON2 in the pathobiology of the said diseases. PON3 is least studied. The PON family, to some extent, interacts with acetylcholine esterase (AChE), as both share the same locus, and PONs degrade the inhibitors of AChE, especially the organophosphates. This could probably have significant role in the development of Parkinson disease and the prognosis of the treatment of Alzheimer disease by AChE inhibitors.