Anti-amyloidogenic, anti-oxidant and anti-apoptotic role of gelsolin in Alzheimer's disease.
Fibrillar amyloid beta-protein (Abeta) is a major component of amyloid plaques in the brains of individuals with Alzheimer's disease (AD) and of adults with Down syndrome (DS). Gelsolin, a cytoskeletal protein, is present both intracellularly (cytoplasmic form) and extracellularly (secretory form in biological fluids). These two forms of gelsolin differ from each other in length and in cysteinyl thiol groups. Previous studies from our and other groups have identified the anti-amyloidogenic role of gelsolin in AD. Our studies showed that both plasma and cytosolic gelsolin bind to Abeta, and that gelsolin inhibits the fibrillization of Abeta and solubilizes preformed fibrils of Abeta. Other studies have shown that peripheral administration of plasma gelsolin or transgene expression of plasma gelsolin can reduce amyloid load in the transgenic mouse model of AD. Our recent studies showed that gelsolin expression increases in cells in response to oxidative stress. Oxidative damage is considered a major feature in the pathophysiology of AD. Abeta not only can induce oxidative stress, but also its generation is increased as a result of oxidative stress. In this article, we review evidence of gelsolin as an anti-amyloidogenic agent that can reduce amyloid load by acting as an inhibitor of Abeta fibrillization, and as an antioxidant and anti-apoptotic protein.
Chauhan
Ved
V
New York State Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, New York, 10314, USA. ved.chauhan@omr.state.ny.us
Ji
Lina
L
Chauhan
Abha
A
D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology*; D000686:Amyloidosis / Q000378:metabolism / Q000473:pathology; D000975:Antioxidants / Q000378:metabolism*; D017209:Apoptosis / Q000502:physiology*; D018260:Gelsolin / Q000378:metabolism*; D006801:Humans
D000975:Antioxidants; D018260:Gelsolin