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Altered cell‐matrix associated ADAM proteins in Alzheimer disease
Author(s) -
Gerst Jennifer L.,
Raina Arun K.,
Pirim Ibrahim,
McShea Andrew,
Harris Peggy L.R.,
Siedlak Sandra L.,
Takeda Atsushi,
Petersen Robert B.,
Smith Mark A.
Publication year - 2000
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/(sici)1097-4547(20000301)59:5<680::aid-jnr11>3.0.co;2-6
Subject(s) - disintegrin , alzheimer's disease , biology , integrin , microbiology and biotechnology , senile plaques , cell cycle , adam10 , metalloproteinase , disease , cell , neuroscience , matrix metalloproteinase , medicine , pathology , genetics
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, mem‐ brane‐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 neurofibrillary 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. J. Neurosci. Res. 59:680–684, 2000 © 2000 Wiley‐Liss, Inc.