title: An Enzyme from Aristolochia indica Destabilizes Fibrin-β Amyloid Co-Aggregate: Implication in Cerebrovascular Diseases.
abstract: Fibrinogen and β-amyloid (Aβ) peptide independently form ordered aggregates but in combination, they form disordered structures which are resistant to fibrinolytic enzymes like plasmin and cause severity in cerebral amyloid angiopathy (CAA). A novel enzyme of 31.3 kDa has been isolated from the root of the medicinal plant Aristolochia indica that showed fibrinolytic as well as fibrin-Aβ co-aggregate destabilizing properties. This enzyme is functionally distinct from plasmin. Thrombolytic action of the enzyme was demonstrated in rat model. The potency of the plant enzyme in degrading fibrin and fibrin-plasma protein (Aβ, human serum albumin, lysozyme, transthyretin and fibronectin) co-aggregates was demonstrated by atomic force microscopy, scanning electron microscopy and confocal microscopy that showed better potency of the plant enzyme as compared to plasmin. Moreover, the plant enzyme inhibited localization of the co-aggregate inside SH-SY5Y human neuroblastoma cells and also co-aggregate induced cytotoxicity. Plasmin was inefficient in this respect. In the background of limited options for fragmentation of these co-aggregates, the plant enzyme may appear as a potential proteolytic enzyme.
authors.affiliation: Division of Structural Biology and Bioinformatics, CSIR -Indian Institute of Chemical Biology, Jadavpur, Kolkata, 700032, India.
authors.forename: Payel
authors.initials: P
authors.lastname: Bhattacharjee
authors.affiliation: Division of Structural Biology and Bioinformatics, CSIR -Indian Institute of Chemical Biology, Jadavpur, Kolkata, 700032, India.
authors.forename: Debasish
authors.initials: D
authors.lastname: Bhattacharyya
mesh_terms: D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity; D000818:Animals; D030022:Aristolochia / Q000201:enzymology*; D045744:Cell Line, Tumor; D002561:Cerebrovascular Disorders / Q000188:drug therapy* / Q000378:metabolism; D004795:Enzyme Stability; D005337:Fibrin / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity; D005342:Fibrinolysis / Q000187:drug effects; D006801:Humans; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity; D010936:Plant Extracts / Q000494:pharmacology* / Q000627:therapeutic use; D066329:Protein Aggregates / Q000187:drug effects*; D059748:Proteolysis / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013927:Thrombosis / Q000188:drug therapy
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D010936:Plant Extracts; D066329:Protein Aggregates; C075222:amyloid beta-protein (1-42); D005337:Fibrin