TY - JOUR
T1 - β-Amyloid precursor protein mismetabolism and loss of calcium homeostasis in Alzheimer's disease
AU - Barger, S. W.
AU - Smith-Swintosky, V. L.
AU - Rydel, R. E.
AU - Mattson, M. P.
PY - 1993
Y1 - 1993
N2 - The suspected involvement of the,B-amyloid precursor protein (βAPP) in the etiology of Alzheimer's disease (AD) has been strengthened by recent genetic evidence, but pursuit of the mechanisms involved will initially require basic cell biology approaches. Several studies have concentrated on toxic activities of β-amyloid peptide (βAP) itself, illuminating its contributions to excitotoxicity and calcium-mediated degeneration in general We now know that generation of βAP from βAPP also compromises the production of an important set of trophic factors: the secreted forms of βAPP (APP(S)), which may act - ironically - by conferring protection from calcium-mediated insults. Therefore, conditions which contribute to the formation of βAP (possibly including ischemia) not only produce an agent which exacerbates calcium-mediated cell death, but also reduce the levels of one of the few factors able to rescue calcium homeostasis. The implications of these postulates and their relationship to the process of aging are discussed.
AB - The suspected involvement of the,B-amyloid precursor protein (βAPP) in the etiology of Alzheimer's disease (AD) has been strengthened by recent genetic evidence, but pursuit of the mechanisms involved will initially require basic cell biology approaches. Several studies have concentrated on toxic activities of β-amyloid peptide (βAP) itself, illuminating its contributions to excitotoxicity and calcium-mediated degeneration in general We now know that generation of βAP from βAPP also compromises the production of an important set of trophic factors: the secreted forms of βAPP (APP(S)), which may act - ironically - by conferring protection from calcium-mediated insults. Therefore, conditions which contribute to the formation of βAP (possibly including ischemia) not only produce an agent which exacerbates calcium-mediated cell death, but also reduce the levels of one of the few factors able to rescue calcium homeostasis. The implications of these postulates and their relationship to the process of aging are discussed.
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U2 - 10.1111/j.1749-6632.1993.tb23045.x
DO - 10.1111/j.1749-6632.1993.tb23045.x
M3 - Article
C2 - 8239276
AN - SCOPUS:0027421612
SN - 0077-8923
VL - 695
SP - 158
EP - 164
JO - Annals of the New York Academy of Sciences
JF - Annals of the New York Academy of Sciences
ER -