Amyloid beta degradation: a challenging task for brain peptidases.
Amyloid beta (Abeta) accumulates in the neuropil and within the walls of cerebral vessels in association with normal aging, dementia or stroke. Abeta is released from its precursor protein as soluble monomeric species yet, under pathological conditions, it self-aggregates to form soluble oligomers or insoluble fibrils that may be toxic to neurons and vascular cells. Abeta levels could be lowered by inhibiting its generation or by promoting its clearance by transport or degradation. Here we will summarize recent findings on brain proteases capable of degrading Abeta, with a special focus on those enzymes for which there is genetic, transgenic or biochemical evidence supporting a role in the proteolysis of Abeta in vivo.
Morelli
Laura
L
Instituto de Química y Fisicoquímica Biológicas, CONICET, Cátedra de Química Biológica Patológica, Departamento de Química Biológica, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina.
Bulloj
Ayelén
A
Leal
María Celeste
MC
Castaño
Eduardo M
EM
D000544:Alzheimer Disease / Q000201:enzymology*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism; D001921:Brain / Q000201:enzymology*; D000072396:Endothelin-Converting Enzymes; D006801:Humans; D007339:Insulysin / Q000378:metabolism; D008666:Metalloendopeptidases / Q000378:metabolism; D015260:Neprilysin / Q000378:metabolism; D010447:Peptide Hydrolases / Q000378:metabolism*; D013379:Substrate Specificity
D016229:Amyloid beta-Peptides; D010447:Peptide Hydrolases; D016282:Aspartic Acid Endopeptidases; D008666:Metalloendopeptidases; D015260:Neprilysin; D007339:Insulysin; D000072396:Endothelin-Converting Enzymes