Abstract
Alterations in cell-matrix 'contact' are often related to a disruption of cell cycle regulation and, as such, occur variously in neoplasia. Given the recent findings showing cell cycle alterations in Alzheimer disease, we undertook a study of ADAM-1 and 2 (A Disintegrin And Metalloprotease), developmentally-regulated, integrin-binding, membrane-bound metalloproteases. Our results show that whereas ADAM-1 and 2 are found in susceptible hippocampal neurons in Alzheimer disease, these proteins were not generally increased in similar neuronal populations in younger or age-matched controls except in association with age-related neurofibriliary alterations. This increase in both ADAM-1 and 2 in cases of Alzheimer disease was verified by immunoblot analysis (P < 0.05). An ADAM-induced loss of matrix integration would effectively 'reset' the mitotic clock and thereby stimulate re-entry into the cell cycle in neurons in Alzheimer disease. Furthermore, given the importance of integrins in maintaining short-term memory, alterations in ADAM proteins or their proteolytic activity could also play a proximal role in the clinico-pathological manifestations of Alzheimer disease. (C) 2000 Wiley- Liss, Inc.
Original language | English |
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Pages (from-to) | 680-684 |
Number of pages | 5 |
Journal | Journal of Neuroscience Research |
Volume | 59 |
Issue number | 5 |
DOIs | |
Publication status | Published - 2000 |
Externally published | Yes |
Keywords
- ADAM-1
- ADAM-2
- Alzheimer disease
- Mitosis
- Neoplasia
ASJC Scopus subject areas
- Cellular and Molecular Neuroscience