14 research outputs found
Intraarterial Digital Subtraction Angiography for Postoperative Determination of Aortocoronary Bypass Graft Patency
Evaluation of sensory acceptability and storage stability of frozen carrot based dessert
Complement component C1q inhibits β-amyloid- and serum amyloid P-induced neurotoxicity via caspase- and calpain-independent mechanisms
Effect of Dimethyl sulfoxide (DMSO) and egg yolk on sperm motility, fertility and hatching rates of depik Rasbora tawarensis
Combined effect of vacuum and different freezing methods on the quality parameters of cherry tomato (Lycopersicon esculentum var. Cerasiforme)
Molecular dissection of Alzheimer's disease neuropathology by depletion of serum amyloid P component
New therapeutic approaches in Alzheimer's disease are urgently needed. The normal plasma protein, serum amyloid P component (SAP), is always present in cerebrospinal fluid (CSF) and in the pathognomonic lesions of Alzheimer's disease, cerebrovascular and intracerebral Aβ amyloid plaques and neurofibrillary tangles, as a result of its binding to amyloid fibrils and to paired helical filaments, respectively. SAP itself may also be directly neurocytotoxic. Here, in this unique study in Alzheimer's disease of the bis(d-proline) compound, (R)-1-[6-[(R)-2-carboxy-pyrrolidin-1-yl]-6-oxo-hexanoyl]pyrrolidine-2-carboxylic acid (CPHPC), we observed depletion of circulating SAP and also remarkable, almost complete, disappearance of SAP from the CSF. We demonstrate that SAP depletion in vivo is caused by CPHPC cross-linking pairs of SAP molecules in solution to form complexes that are immediately cleared from the plasma. We have also solved the structure of SAP complexed with phosphothreonine, its likely ligand on hyperphosphorylated τ protein. These results support further clinical study of SAP depletion in Alzheimer's disease and potentially other neurodegenerative diseases