title: Exchangeable GTP binding site of the beta-subunit of brain tubulin in Alzheimer disease.
abstract: A major cytoskeletal and molecular change of yet unknown mechanism is the accumulation of argentophilic neurofibrillary tangles in certain selected neurons of the aged human brain, especially the Alzheimer disease/senile dementia of the Alzheimer type (AD/SDAT). Increasing evidence suggests an association between neurofibrillary tangles and a defective microtubule (MT) assembly in AD/SDAT brain. Tubulin, the basic unit of MT is an alpha-beta heterodimer protein of about 55,000 molecular weight each. The beta subunit of tubulin has an exchangeable (E) binding site for guanosine triphosphate (GTP) which in the presence of microtubule-associated proteins (MAPS) promotes the MT assembly. The 8-azido GTP, a photoaffinity analog of GTP, which has been proven to mimic the natural ligand in promoting MT assembly, was used to examine the GTP binding of beta- tubulin in AD brain. Preliminary studies revealed a minimal photoinsertion into the beta-subunit of tubulin in AD/SDAT brain homogenate. Furthermore, the exchangeable GTP binding site was also unavailable in brain tubulin isolated from most of the AD/SDAT cases.
authors.affiliation: New York State Institute for Basic Research in Developmental Disabilities, Staten Island 10314.
authors.forename: S
authors.initials: S
authors.lastname: Khatoon
authors.forename: K
authors.initials: K
authors.lastname: Iqbal
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism*; D001665:Binding Sites; D001921:Brain / Q000378:metabolism / Q000473:pathology; D006160:Guanosine Triphosphate / Q000378:metabolism*; D006801:Humans; D008870:Microtubules / Q000378:metabolism; D009454:Neurofibrils / Q000378:metabolism*; D014404:Tubulin / Q000378:metabolism*
chemical_list: D014404:Tubulin; D006160:Guanosine Triphosphate