Abnormal post-translational and extracellular processing of brevican in plaque-bearing mice over-expressing APPsw.

摘要: Aggregation of amyloid-β in the forebrain Alzheimer's disease subjects may disturb molecular organization extracellular microenvironment that modulates neural and synaptic plasticity. Proteoglycans are major components this environment. To test hypothesis amyloid-β, or another amyloid precursor protein dependent mechanism modifies accumulation and/or turnover proteoglycans, we examined whether expression processing brevican, an abundant extracellular, chondroitin sulfate-bearing proteoglycan, were altered brains amyloid-β-depositing transgenic mice (APPsw) as a model disease. The size sulfate chains attached to brevican was smaller hippocampal tissue from APPsw bearing deposits compared non-transgenic mice, likely due changes chains. Also, abundance proteolytic fragment markedly diminished extracts several telencephalic regions yet these immunoreactive fragments appeared accumulate adjacent plaque edge. These results suggest exert inhibitory effects on cleavage mechanisms responsible for synthesis proteoglycans. Since proteoglycans stabilize structure inhibit plasticity, defective observed amyloid-β-bearing potentially end-stage human disease, contribute deficient