Role of the 39-kDa receptor-associated protein (RAP) in Alzheimer's disease

摘要: Alzheimer’s disease (AD) is the most common form of dementia that gradually worsens over time and leads to death. AD characterized by an accumulation β-amyloid protein (Aβ) in brain. Recently, 39-kDa receptor-associated (RAP) has been implicated pathology. RAP found mainly endoplasmic reticulum (ER) functions as a chaperone for maturation trafficking low density lipoprotein (LDL) receptor family. Polymorphisms gene have associated with increased risk AD. Two studies shown down-regulation expression exacerbates Aβ pathology transgenic mouse models AD, suggesting may important role production clearance. It also binds strongly Aβ, leading inhibition aggregation neurotoxicity. Furthermore, recent study level significantly decreased brain compared healthy controls. This aimed identify region which effect over-expression treatment on APP metabolism production. The possibility can bind human CSF was examined. To determine Aβ-binding RAP, in-vitro assay established validated Aβ-self association, based binding biotin labelled Aβ42 synthetic seeded wells microplates. identified measuring association presence different fragments. results indicated site located between amino acid residues 206 216 sequence loop domains D2 D3. examine metabolism, two strategies were used. first strategy involved sweAPP-CHO sweAPP-SH-SY5Y cells, after processing analysed. As second strategy, examined primary cortical neurons derived from Tg2576 mice. showed or had no significant total APP. However, levels sAPPβ, C99 C83 RAP-transfected cells. suggest could decrease decreasing β-cleavage. Therefore, contribute pathogenesis Attempts if not successful; preliminary results, however, suggested Clusterin/CLU main CSF. Taken together, these data protective factor against disease.