Unaltered Secretion of β-Amyloid Precursor Protein in Gelatinase A (Matrix Metalloproteinase 2)-deficient Mice
Year: 1997
Type: article
Abstract: The beta-amyloid peptide, which forms extracellular cerebral deposits in Alzheimer's disease, is derived from a large membrane-spanning glycoprotein referred to as the beta-amyloid precursor protein (APP). The APP is normally cleaved within the beta-amyloid region by a putative proteinase (alpha-secretase) to generate large soluble amino-terminal derivatives of APP, and this event prevents the beta-amyloid peptide formation. It has been suggested that the gelatinase A (matrix metalloproteinase 2, a 72-kDa type IV collagenase) may act either as alpha-secretase or as beta-secretase. Mice devoid of gelatinase A generated by gene targeting develop normally, except for a subtle delay in their growth, thus providing a useful system to examine the role of gelatinase A in the cleavage and secretion of APP in vivo. We show here that APP is cleaved within the beta-amyloid region and secreted into the extracellular milieu of brain and cultured fibroblasts without gelatinase A activity. The data suggest that gelatinase A does not play an essential role in the generation and release of soluble derivatives of APP at physiological conditions.
Source: Journal of Biological Chemistry
Authors: Takeshi Itoh, Toshio Ikeda, Hiroshi Gomi, Shinobu Nakao, Toshiharu Suzuki, Shigeyoshi Itohara
Institutions: Kyoto University, The University of Tokyo
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $3,430
Funder: Shionogi
OpenAlex ID: W2059659414