Melatonin reverses the profibrillogenic activity of apolipoprotein E4 on the alzheimer amyloid Aβ peptidet

B. Poeggeler, L. Miravalle, M. G. Zagorski, T. Wisniewski, Y. J. Chyan, Y. Zhang, H. Shao, T. Bryant-Thomas, Ruben Vidal, B. Frangione, J. Ghiso, M. A. Pappolla

Research output: Contribution to journalArticle

109 Citations (Scopus)

Abstract

Inheritance of apoE4 is a strong risk factor for the development of late-onset sporadic Alzheimer's disease (AD). Several lines of evidence suggest that apoE4 binds to the Alzheimer Aβ protein and, under certain experimental conditions, promotes formation of β-sheet structures and amyloid fibrils. Deposition of amyloid fibrils is a critical step in the development of AD. We report here that addition of melatonin to Aβ in the presence of apoE resulted in a potent isoform-specific inhibition of fibril formation, the extent of which was far greater than that of the inhibition produced by melatonin alone. This effect was structure-dependent and unrelated to the antioxidant properties of melatonin, since it could be reproduced neither with the structurally related indole N-acetyl-5-hydroxytryptamine nor with the antioxidants ascorbate, α-tocophenol, and PBN. The enhanced inhibitory effects of melatonin and apoE were lost when bovine serum albumin was substituted for apoE. In addition, Aβ in combination with apoE was highly neurotoxic (apoE4 > apoE3) to neuronal cells in culture, and this activity was also prevented by melatonin. These findings suggest that reductions in brain melatonin, which occur during aging, may contribute to a proamyloidogenic microenvironment in the aging brain.

Original languageEnglish
Pages (from-to)14995-15001
Number of pages7
JournalBiochemistry
Volume40
Issue number49
DOIs
StatePublished - Dec 11 2001

Fingerprint

Apolipoprotein E4
Melatonin
Amyloid
Apolipoproteins E
Brain
Alzheimer Disease
Antioxidants
Aging of materials
Apolipoprotein E3
Bovine Serum Albumin
Protein Isoforms
Cell Culture Techniques

ASJC Scopus subject areas

  • Biochemistry

Cite this

Poeggeler, B., Miravalle, L., Zagorski, M. G., Wisniewski, T., Chyan, Y. J., Zhang, Y., ... Pappolla, M. A. (2001). Melatonin reverses the profibrillogenic activity of apolipoprotein E4 on the alzheimer amyloid Aβ peptidet. Biochemistry, 40(49), 14995-15001. https://doi.org/10.1021/bi0114269

Melatonin reverses the profibrillogenic activity of apolipoprotein E4 on the alzheimer amyloid Aβ peptidet. / Poeggeler, B.; Miravalle, L.; Zagorski, M. G.; Wisniewski, T.; Chyan, Y. J.; Zhang, Y.; Shao, H.; Bryant-Thomas, T.; Vidal, Ruben; Frangione, B.; Ghiso, J.; Pappolla, M. A.

In: Biochemistry, Vol. 40, No. 49, 11.12.2001, p. 14995-15001.

Research output: Contribution to journalArticle

Poeggeler, B, Miravalle, L, Zagorski, MG, Wisniewski, T, Chyan, YJ, Zhang, Y, Shao, H, Bryant-Thomas, T, Vidal, R, Frangione, B, Ghiso, J & Pappolla, MA 2001, 'Melatonin reverses the profibrillogenic activity of apolipoprotein E4 on the alzheimer amyloid Aβ peptidet', Biochemistry, vol. 40, no. 49, pp. 14995-15001. https://doi.org/10.1021/bi0114269
Poeggeler B, Miravalle L, Zagorski MG, Wisniewski T, Chyan YJ, Zhang Y et al. Melatonin reverses the profibrillogenic activity of apolipoprotein E4 on the alzheimer amyloid Aβ peptidet. Biochemistry. 2001 Dec 11;40(49):14995-15001. https://doi.org/10.1021/bi0114269
Poeggeler, B. ; Miravalle, L. ; Zagorski, M. G. ; Wisniewski, T. ; Chyan, Y. J. ; Zhang, Y. ; Shao, H. ; Bryant-Thomas, T. ; Vidal, Ruben ; Frangione, B. ; Ghiso, J. ; Pappolla, M. A. / Melatonin reverses the profibrillogenic activity of apolipoprotein E4 on the alzheimer amyloid Aβ peptidet. In: Biochemistry. 2001 ; Vol. 40, No. 49. pp. 14995-15001.
@article{1b163fc6a4144c28b17c6535ad21bba0,
title = "Melatonin reverses the profibrillogenic activity of apolipoprotein E4 on the alzheimer amyloid Aβ peptidet",
abstract = "Inheritance of apoE4 is a strong risk factor for the development of late-onset sporadic Alzheimer's disease (AD). Several lines of evidence suggest that apoE4 binds to the Alzheimer Aβ protein and, under certain experimental conditions, promotes formation of β-sheet structures and amyloid fibrils. Deposition of amyloid fibrils is a critical step in the development of AD. We report here that addition of melatonin to Aβ in the presence of apoE resulted in a potent isoform-specific inhibition of fibril formation, the extent of which was far greater than that of the inhibition produced by melatonin alone. This effect was structure-dependent and unrelated to the antioxidant properties of melatonin, since it could be reproduced neither with the structurally related indole N-acetyl-5-hydroxytryptamine nor with the antioxidants ascorbate, α-tocophenol, and PBN. The enhanced inhibitory effects of melatonin and apoE were lost when bovine serum albumin was substituted for apoE. In addition, Aβ in combination with apoE was highly neurotoxic (apoE4 > apoE3) to neuronal cells in culture, and this activity was also prevented by melatonin. These findings suggest that reductions in brain melatonin, which occur during aging, may contribute to a proamyloidogenic microenvironment in the aging brain.",
author = "B. Poeggeler and L. Miravalle and Zagorski, {M. G.} and T. Wisniewski and Chyan, {Y. J.} and Y. Zhang and H. Shao and T. Bryant-Thomas and Ruben Vidal and B. Frangione and J. Ghiso and Pappolla, {M. A.}",
year = "2001",
month = "12",
day = "11",
doi = "10.1021/bi0114269",
language = "English",
volume = "40",
pages = "14995--15001",
journal = "Biochemistry",
issn = "0006-2960",
publisher = "American Chemical Society",
number = "49",

}

TY - JOUR

T1 - Melatonin reverses the profibrillogenic activity of apolipoprotein E4 on the alzheimer amyloid Aβ peptidet

AU - Poeggeler, B.

AU - Miravalle, L.

AU - Zagorski, M. G.

AU - Wisniewski, T.

AU - Chyan, Y. J.

AU - Zhang, Y.

AU - Shao, H.

AU - Bryant-Thomas, T.

AU - Vidal, Ruben

AU - Frangione, B.

AU - Ghiso, J.

AU - Pappolla, M. A.

PY - 2001/12/11

Y1 - 2001/12/11

N2 - Inheritance of apoE4 is a strong risk factor for the development of late-onset sporadic Alzheimer's disease (AD). Several lines of evidence suggest that apoE4 binds to the Alzheimer Aβ protein and, under certain experimental conditions, promotes formation of β-sheet structures and amyloid fibrils. Deposition of amyloid fibrils is a critical step in the development of AD. We report here that addition of melatonin to Aβ in the presence of apoE resulted in a potent isoform-specific inhibition of fibril formation, the extent of which was far greater than that of the inhibition produced by melatonin alone. This effect was structure-dependent and unrelated to the antioxidant properties of melatonin, since it could be reproduced neither with the structurally related indole N-acetyl-5-hydroxytryptamine nor with the antioxidants ascorbate, α-tocophenol, and PBN. The enhanced inhibitory effects of melatonin and apoE were lost when bovine serum albumin was substituted for apoE. In addition, Aβ in combination with apoE was highly neurotoxic (apoE4 > apoE3) to neuronal cells in culture, and this activity was also prevented by melatonin. These findings suggest that reductions in brain melatonin, which occur during aging, may contribute to a proamyloidogenic microenvironment in the aging brain.

AB - Inheritance of apoE4 is a strong risk factor for the development of late-onset sporadic Alzheimer's disease (AD). Several lines of evidence suggest that apoE4 binds to the Alzheimer Aβ protein and, under certain experimental conditions, promotes formation of β-sheet structures and amyloid fibrils. Deposition of amyloid fibrils is a critical step in the development of AD. We report here that addition of melatonin to Aβ in the presence of apoE resulted in a potent isoform-specific inhibition of fibril formation, the extent of which was far greater than that of the inhibition produced by melatonin alone. This effect was structure-dependent and unrelated to the antioxidant properties of melatonin, since it could be reproduced neither with the structurally related indole N-acetyl-5-hydroxytryptamine nor with the antioxidants ascorbate, α-tocophenol, and PBN. The enhanced inhibitory effects of melatonin and apoE were lost when bovine serum albumin was substituted for apoE. In addition, Aβ in combination with apoE was highly neurotoxic (apoE4 > apoE3) to neuronal cells in culture, and this activity was also prevented by melatonin. These findings suggest that reductions in brain melatonin, which occur during aging, may contribute to a proamyloidogenic microenvironment in the aging brain.

UR - http://www.scopus.com/inward/record.url?scp=0035846613&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035846613&partnerID=8YFLogxK

U2 - 10.1021/bi0114269

DO - 10.1021/bi0114269

M3 - Article

VL - 40

SP - 14995

EP - 15001

JO - Biochemistry

JF - Biochemistry

SN - 0006-2960

IS - 49

ER -