Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.22.32 (bromelain)
 1,025 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Peptides derived from proteolytic degradation of the amyloid precursor protein, e.g., amyloid beta (A beta), are considered to be central to the pathology of Alzheimer's disease (AD). Soluble A beta is present in measurable concentrations in cerebrospinal fluid and blood. There are indications that soluble A beta present in circulation can cross the blood-brain barrier via transcytosis mediated by brain capillary endothelial cells. It implies that A beta originating from circulation may contribute to vascular and parenchymal A beta deposition in AD. Enhancing of A beta catabolism mediated by proteolytic degradation or receptor-mediated endocytosis could be a key mechanism to maintain low concentrations of soluble A beta. To launch A beta clearance we have exploited the A beta-degrading activity of diverse alpha 2-macroglobulin (alpha 2-M)-proteinase complexes. Complexes with trypsin, alpha-chymotrypsin, and bromelain strongly degrade (125)I-A beta 1--42 whereas complexes with endogenous proteinases, e.g., plasmin and prostate-specific antigen, were not effective. A beta degradation by the complexes was not inhibited by alpha 1-antichymotrypsin and soybean trypsin inhibitor which normally would inactivate the free serine proteinases. A prerequisite for A beta degradation is its binding to specific binding sites in alpha 2-M that may direct A beta to the active site of the caged proteinase. Ex vivo, enhanced degradation of (125)I-A beta 1--42 in blood could be achieved upon oral administration of high doses of proteinases to volunteers. These results suggest that up-regulation of A beta catabolism could probably reduce the risk of developing AD by preventing A beta accumulation in brain and vasculature.
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PMID:Alpha 2-macroglobulin-mediated degradation of amyloid beta 1--42: a mechanism to enhance amyloid beta catabolism. 1116 27

Effects of amyloid beta peptide 1-40 (Abeta) and of plant cysteine proteases bromelain and papain on the high-affinity uptake of choline (HACU) and the specific binding of [3H]hemicholinium-3 ([3H]HC-3) have been investigated on hippocampal synaptosomes from young adult male Wistar rats under basal and stimulated conditions (55 mM KCl). Depolarization increased significantly the HACU levels (the changes were predominantly in Vmax) and mildly the [3H]HC-3 binding (the changes especially in K(D)). Nonaggregated Abeta at low nM concentrations suppressed the depolarization effects but was ineffective under basal conditions during a short-term incubation. Higher microM concentrations decreased the HACU and binding under basal conditions in a time-dependent manner. The binding changes were firstly associated with alterations in K(D) and secondarily were accompanied also by a drop in Bmax. The results suggest that Abeta directly influences high-affinity carriers, inhibits their transport activity and enhances their sensitivity to proteoLytic cleavage. Stimulation increases the sensitivity of carriers to the interaction with Abeta.
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PMID:Amyloid beta peptide 1-40 and the function of rat hippocampal hemicholinium-3 sensitive choline carriers: effects of a proteolytic degradation in vitro. 1149 43