ALZHEIMER'S DISEASE AND DEMENTIA WITH LEWY BODIES: SPECIAL FOCUS ON THE ROLE OF SERPINS

摘要: Serine protease inhibitors (Serpins) are involved in the pathogenesis of neurodegenerative dementia, including two most common types, Alzheimer’s disease (AD) and dementia with Lewy bodies (DLB). The pathological characteristics AD include senile plaques, mainly composed aggregated amyloid-beta peptide (Abeta1-42), but also serpins, neurofibrillary tangles hyperphosphorylated tau protein. Pathological hallmarks DLB aggregates alpha-synuclein (Lewy bodies), however, co-existing pathology is frequently found. In present work, we have investigated role three namely alpha1-antichymyotrypsin, alpha1-antitrypsin neuroserpin, context DLB. We shown that alpha1-antichymotrypsin: (i) renders oligomer formation profile incubated Abeta1-42, favouring dimer formation; (ii) under certain conditions appears to protect Abeta1-42 from chymotrypsin digestion and;(iii) combination soluble forms significantly affects global gene expression primary fetal human astrocytes; (iv) can influence binding and, potentially, uptake adult astrocytes. clinical studies have: for first time, determined cerebrospinal fluid levels neuroserpin established a link as higher were found patients than non-demented controls patients; showed plasma alpha1-antichymotrypsin correlate lower cognitive function AD, respectively; (iii) intercellular adhesion molecule-1 platelet endothelial cell molecule-1. Our findings support statement inflammatory vascular mechanisms suggest serpins likely processes leading dysfunction. Further research needed assess distinct actions neurodegeneration dementia. (Less)