Abstract
Previously, we found that amyloid β-protein (Aβ)1-42 exhibits neurotoxicity, while Aβ1-40 serves as an antioxidant molecule by quenching metal ions and inhibiting metal-mediated oxygen radical generation. Here, we show another neuroprotective action of nonamyloidogenic Aβ1-40 against Aβ1-42-induced neurotoxicity in culture and in vivo. Neuronal death was induced by Aβ1-42 at concentrations higher than 2 μm, which was prevented by concurrent treatment with Aβ1-40 in a dose-dependent manner. However, metal chelators did not prevent Aβ1-42-induced neuronal death. Circular dichroism spectroscopy showed that Aβ1-40 inhibited the β-sheet transformation of Aβ1-42. Thioflavin-T. assay and electron microscopy analysis revealed that Aβ1-40 inhibited the fibril formation of Aβ1-42. In contrast, Aβ1-16, Aβ25-35, and Aβ40-1 did not inhibit the fibril formation of Aβ1-42 nor prevent Aβ1-42-induced neuronal death. Aβ1-42 injection into the rat entorhinal cortex (EC) caused the hyperphosphorylation of tau on both sides of EC and hippocampus and increased the number of glial fibrillary acidic protein (GFAP)-positive astrocytes in the ipsilateral EC, which were prevented by the concurrent injection of Aβ1-40. These results indicate that Aβ1-40 protects neurons from Aβ1-42-induced neuronal damage in vitro and in vivo, not by sequestrating metals, but by inhibiting the β-sheet transformation and fibril formation of Aβ1-42. Our data suggest a mechanism by which elevated Aβ1-42/Aβ1-40 ratio accelerates the development of Alzheimer's disease (AD) in familial AD.
| Original language | English |
|---|---|
| Pages (from-to) | 609-619 |
| Number of pages | 11 |
| Journal | Journal of Neurochemistry |
| Volume | 87 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - 2003 Nov |
| Externally published | Yes |
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Keywords
- Alzheimer's disease
- Amyloid β-protein
- Monomer
- Neuroprotection
- Oligomer
- Tau phosphorylation
ASJC Scopus subject areas
- Biochemistry
- Cellular and Molecular Neuroscience
Cite this
Amyloid β-protein (Aβ)1-40 protects neurons from damage induced by Aβ1-42 in culture and in rat brain. / Zou, Kun; Kim, Daesung; Kakio, Atsuko; Byun, Kyunghee; Gong, Jian Sheng; Kim, Jaewoo; Kim, Myeungju; Sawamura, Naoya; Nishimoto, Sei Ichi; Matsuzaki, Katsumi; Lee, Bonghee; Yanagisawa, Katsuhiko; Michikawa, Makoto.
In: Journal of Neurochemistry, Vol. 87, No. 3, 11.2003, p. 609-619.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Amyloid β-protein (Aβ)1-40 protects neurons from damage induced by Aβ1-42 in culture and in rat brain
AU - Zou, Kun
AU - Kim, Daesung
AU - Kakio, Atsuko
AU - Byun, Kyunghee
AU - Gong, Jian Sheng
AU - Kim, Jaewoo
AU - Kim, Myeungju
AU - Sawamura, Naoya
AU - Nishimoto, Sei Ichi
AU - Matsuzaki, Katsumi
AU - Lee, Bonghee
AU - Yanagisawa, Katsuhiko
AU - Michikawa, Makoto
PY - 2003/11
Y1 - 2003/11
N2 - Previously, we found that amyloid β-protein (Aβ)1-42 exhibits neurotoxicity, while Aβ1-40 serves as an antioxidant molecule by quenching metal ions and inhibiting metal-mediated oxygen radical generation. Here, we show another neuroprotective action of nonamyloidogenic Aβ1-40 against Aβ1-42-induced neurotoxicity in culture and in vivo. Neuronal death was induced by Aβ1-42 at concentrations higher than 2 μm, which was prevented by concurrent treatment with Aβ1-40 in a dose-dependent manner. However, metal chelators did not prevent Aβ1-42-induced neuronal death. Circular dichroism spectroscopy showed that Aβ1-40 inhibited the β-sheet transformation of Aβ1-42. Thioflavin-T. assay and electron microscopy analysis revealed that Aβ1-40 inhibited the fibril formation of Aβ1-42. In contrast, Aβ1-16, Aβ25-35, and Aβ40-1 did not inhibit the fibril formation of Aβ1-42 nor prevent Aβ1-42-induced neuronal death. Aβ1-42 injection into the rat entorhinal cortex (EC) caused the hyperphosphorylation of tau on both sides of EC and hippocampus and increased the number of glial fibrillary acidic protein (GFAP)-positive astrocytes in the ipsilateral EC, which were prevented by the concurrent injection of Aβ1-40. These results indicate that Aβ1-40 protects neurons from Aβ1-42-induced neuronal damage in vitro and in vivo, not by sequestrating metals, but by inhibiting the β-sheet transformation and fibril formation of Aβ1-42. Our data suggest a mechanism by which elevated Aβ1-42/Aβ1-40 ratio accelerates the development of Alzheimer's disease (AD) in familial AD.
AB - Previously, we found that amyloid β-protein (Aβ)1-42 exhibits neurotoxicity, while Aβ1-40 serves as an antioxidant molecule by quenching metal ions and inhibiting metal-mediated oxygen radical generation. Here, we show another neuroprotective action of nonamyloidogenic Aβ1-40 against Aβ1-42-induced neurotoxicity in culture and in vivo. Neuronal death was induced by Aβ1-42 at concentrations higher than 2 μm, which was prevented by concurrent treatment with Aβ1-40 in a dose-dependent manner. However, metal chelators did not prevent Aβ1-42-induced neuronal death. Circular dichroism spectroscopy showed that Aβ1-40 inhibited the β-sheet transformation of Aβ1-42. Thioflavin-T. assay and electron microscopy analysis revealed that Aβ1-40 inhibited the fibril formation of Aβ1-42. In contrast, Aβ1-16, Aβ25-35, and Aβ40-1 did not inhibit the fibril formation of Aβ1-42 nor prevent Aβ1-42-induced neuronal death. Aβ1-42 injection into the rat entorhinal cortex (EC) caused the hyperphosphorylation of tau on both sides of EC and hippocampus and increased the number of glial fibrillary acidic protein (GFAP)-positive astrocytes in the ipsilateral EC, which were prevented by the concurrent injection of Aβ1-40. These results indicate that Aβ1-40 protects neurons from Aβ1-42-induced neuronal damage in vitro and in vivo, not by sequestrating metals, but by inhibiting the β-sheet transformation and fibril formation of Aβ1-42. Our data suggest a mechanism by which elevated Aβ1-42/Aβ1-40 ratio accelerates the development of Alzheimer's disease (AD) in familial AD.
KW - Alzheimer's disease
KW - Amyloid β-protein
KW - Monomer
KW - Neuroprotection
KW - Oligomer
KW - Tau phosphorylation
UR - http://www.scopus.com/inward/record.url?scp=0142241380&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0142241380&partnerID=8YFLogxK
U2 - 10.1046/j.1471-4159.2003.02018.x
DO - 10.1046/j.1471-4159.2003.02018.x
M3 - Article
VL - 87
SP - 609
EP - 619
JO - Journal of Neurochemistry
JF - Journal of Neurochemistry
SN - 0022-3042
IS - 3
ER -