TY - JOUR
T1 - Cytochalasins Protect Hippocampal Neurons Against Amyloid β‐Peptide Toxicity
T2 - Evidence that Actin Depolymerization Suppresses Ca2+ Influx
AU - Furukawa, Katsutoshi
AU - Mattson, Mark P.
N1 - Copyright:
Copyright 2016 Elsevier B.V., All rights reserved.
PY - 1995/9
Y1 - 1995/9
N2 - Abstract: Increasing data suggest that the amyloid β‐peptide (Aβ), which accumulates in the brains of Alzheimer's victims, plays a role in promoting neuronal degeneration. Cell culture studies have shown that Aβ can be neurotoxic and recent findings suggest that the mechanism involves destabilization of cellular calcium homeostasis. We now report that cytochalasin D, a compound that depolymerizes actin microfilaments selectively, protects cultured rat hippocampal neurons against Aβ neurotoxicity. Cytochalasin D was effective at concentrations that depolymerized actin (10–100 nM). The elevation of [Ca2+]i induced by Aβ, and the enhancement of [Ca2+]i responses to glutamate in neurons exposed to Aβ, were markedly attenuated in neurons pretreated with cytochalasin D. The protective effect of cytochalasin D appeared to result from a specific effect on actin filaments and reduction in calcium influx, because cytochalasin E, another actin filament‐disrupting agent, also protected neurons against Aβ toxicity; the microtubule‐disrupting agent colchicine was ineffective; cytochalasin D did not protect neurons against the toxicity of hydrogen peroxide. These findings suggest that actin filaments play a role in modulating [Ca2+]i responses to neurotoxic insults and that depolymerization of actin can protect neurons against insults relevant to the pathogenesis of Alzheimer's disease.
AB - Abstract: Increasing data suggest that the amyloid β‐peptide (Aβ), which accumulates in the brains of Alzheimer's victims, plays a role in promoting neuronal degeneration. Cell culture studies have shown that Aβ can be neurotoxic and recent findings suggest that the mechanism involves destabilization of cellular calcium homeostasis. We now report that cytochalasin D, a compound that depolymerizes actin microfilaments selectively, protects cultured rat hippocampal neurons against Aβ neurotoxicity. Cytochalasin D was effective at concentrations that depolymerized actin (10–100 nM). The elevation of [Ca2+]i induced by Aβ, and the enhancement of [Ca2+]i responses to glutamate in neurons exposed to Aβ, were markedly attenuated in neurons pretreated with cytochalasin D. The protective effect of cytochalasin D appeared to result from a specific effect on actin filaments and reduction in calcium influx, because cytochalasin E, another actin filament‐disrupting agent, also protected neurons against Aβ toxicity; the microtubule‐disrupting agent colchicine was ineffective; cytochalasin D did not protect neurons against the toxicity of hydrogen peroxide. These findings suggest that actin filaments play a role in modulating [Ca2+]i responses to neurotoxic insults and that depolymerization of actin can protect neurons against insults relevant to the pathogenesis of Alzheimer's disease.
KW - Actin microfilaments
KW - Alzheimer's disease
KW - Amyloid
KW - Calcium
KW - Cytochalasin
KW - Glutamate
KW - Neurotoxicity
KW - Phalloidin
UR - http://www.scopus.com/inward/record.url?scp=0029165076&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0029165076&partnerID=8YFLogxK
U2 - 10.1046/j.1471-4159.1995.65031061.x
DO - 10.1046/j.1471-4159.1995.65031061.x
M3 - Article
C2 - 7643084
AN - SCOPUS:0029165076
VL - 65
SP - 1061
EP - 1068
JO - Journal of Neurochemistry
JF - Journal of Neurochemistry
SN - 0022-3042
IS - 3
ER -