We have recently identified in a transgenic mouse model of Alzheimer's disease (AD) membrane-type 5-MMP (MT5-MMP) as a new player in Alzheimer's pathogenesis, which displays pro-amyloidogenic features and proteolytic processing of amyloid precursor protein (APP). Another group has reported that MT5-MMP processing of APP may release a novel neurotoxic APP fragment. Although MT5-MMP-mediated APP processing appears to be a key pathogenic step, we hypothesize that MT5-MMP may also contribute to AD pathogenesis through complementary mechanisms that involve the activation of pro-inflammatory pathways and/or APP trafficking.
Keywords: Amyloid precursor protein; Amyloidogenesis; IL-1β; Matrix metalloproteinases; Neurodegenerative disease; Neuroinflammation; Trafficking.