title: The degradation of amyloid beta as a therapeutic strategy in Alzheimer's disease and cerebrovascular amyloidoses.
abstract: The deposition of 4-kDa amyloid beta peptide in the brain is a prominent feature of several human diseases. Such process is heterogeneous in terms of causative factors, biochemical phenotype, localization and clinical manifestations. Amyloid beta accumulates in the neuropil or within the walls of cerebral vessels, and associates with dementia or stroke, both hereditary and sporadic. Amyloid beta is normally released by cells as soluble monomeric-dimeric species yet, under pathological conditions, it self-aggregates as soluble oligomers or insoluble fibrils that may be toxic to neurons and vascular cells. Lowering amyloid beta levels may be achieved by inhibiting its generation from the amyloid beta-precursor protein or by promoting its clearance by transport or degradation. We will summarize recent findings on brain proteases capable of degrading amyloid beta with a special focus on those enzymes for which there is genetic, transgenic or biochemical evidence suggesting that they may participate in the proteolysis of amyloid beta in vivo. We will also put in perspective their possible utilization as therapeutic agents in amyloid beta diseases.
authors.affiliation: Instituto de Química y Fisicoquímica Biológicas (IQUIFIB), CONICET, Cátedra de Química Biológica Patológica, Departamento de Química Biológica, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Argentina.
authors.forename: Laura
authors.initials: L
authors.lastname: Morelli
authors.forename: Ramiro
authors.initials: R
authors.lastname: Llovera
authors.forename: Sandra
authors.initials: S
authors.lastname: Ibendahl
authors.forename: Eduardo M
authors.initials: EM
authors.lastname: Castaño
mesh_terms: D000544:Alzheimer Disease / Q000628:therapy*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000686:Amyloidosis / Q000628:therapy*; D001921:Brain / Q000201:enzymology / Q000378:metabolism; D010450:Endopeptidases / Q000378:metabolism; D006801:Humans; D006868:Hydrolysis
chemical_list: D016229:Amyloid beta-Peptides; D010450:Endopeptidases