Antiamyloidogenic and neuroprotective functions of cathepsin B: implications for Alzheimer's disease.
Neuron
; 51(6): 703-14, 2006 Sep 21.
Article
em En
| MEDLINE
| ID: mdl-16982417
ABSTRACT
Alzheimer's disease (AD) may result from the accumulation of amyloid-beta (Abeta) peptides in the brain. The cysteine protease cathepsin B (CatB) is associated with amyloid plaques in AD brains and has been suspected to increase Abeta production. Here, we demonstrate that CatB actually reduces levels of Abeta peptides, especially the aggregation-prone species Abeta1-42, through proteolytic cleavage. Genetic inactivation of CatB in mice with neuronal expression of familial AD-mutant human amyloid precursor protein (hAPP) increased the relative abundance of Abeta1-42, worsening plaque deposition and other AD-related pathologies. Lentivirus-mediated expression of CatB in aged hAPP mice reduced preexisting amyloid deposits, even thioflavin S-positive plaques. Under cell-free conditions, CatB effectively cleaved Abeta1-42, generating C-terminally truncated Abeta peptides that are less amyloidogenic. Thus, CatB likely fulfills antiamyloidogenic and neuroprotective functions. Insufficient CatB activity might promote AD; increasing CatB activity could counteract the neuropathology of this disease.
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Base de dados:
MEDLINE
Assunto principal:
Catepsina B
/
Doença de Alzheimer
/
Amiloide
Limite:
Animals
/
Female
/
Humans
/
Male
Idioma:
En
Ano de publicação:
2006
Tipo de documento:
Article