title: Gelsolin is proteolytically cleaved in the brains of individuals with Alzheimer's disease.
abstract: Gelsolin, a multifunctional actin-binding protein, forms a complex with amyloid-beta protein and reduces the amyloid load in the transgenic mouse model of Alzheimer's disease (AD). Gelsolin consists of six homologous domains, which have specific affinities for phosphatidylinositol 4, 5-bisphosphate, calcium, and actin. During apoptosis, gelsolin is cleaved by the caspase-3 resulting in a 48 kDa carboxyl-terminal fragment (gelsolin-CTF). We report here that gelsolin is significantly cleaved in the frontal cortex of individuals with AD as compared to age-matched controls. A positive correlation was observed between the appearance of gelsolin-CTF in frontal cortex and severity of AD. Gelsolin-CTF was also observed in apoptotic SH-SY5Y cells induced by H2O2 or calcium ionophore A23187. In addition, lipid peroxidation was increased in the frontal cortex of AD suggesting that oxidative stress occurs in AD brain. Taken together, these results suggest that there may be a link among oxidative stress, neuronal apoptosis, and gelsolin cleavage in AD.
authors.affiliation: New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY 10314, USA.
authors.forename: Lina
authors.initials: L
authors.lastname: Ji
authors.forename: Abha
authors.initials: A
authors.lastname: Chauhan
authors.forename: Jerzy
authors.initials: J
authors.lastname: Wegiel
authors.forename: Musthafa M
authors.initials: MM
authors.lastname: Essa
authors.forename: Ved
authors.initials: V
authors.lastname: Chauhan
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D005260:Female; D018260:Gelsolin / Q000378:metabolism*; D006801:Humans; D006868:Hydrolysis; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000502:physiology; D010447:Peptide Hydrolases / Q000378:metabolism
chemical_list: D018260:Gelsolin; D010447:Peptide Hydrolases