Alzheimer β protein mediated oxidative damage of mitochondrial DNA

Prevention by melatonin

Miguel Pappolla, Y. J. Chyan, B. Poeggeler, P. Bozner, J. Ghiso, S. P. LeDoux, G. L. Wilson

Research output: Contribution to journalArticle

75 Citations (Scopus)

Abstract

Most contemporary progress in Alzheimer's disease (AD) stems from the study of a 42-43 amino acid peptide, called the amyloid beta protein (Aβ), as the main neuropathologic marker of the disorder. It has been demonstrated that Aβ has neurotoxic properties and that such effects are mediated by free-radicals. Exposure of neuronal cells to Aβ results in a spectrum of oxidative lesions that are profoundly harmful to neuronal homeostasis. We had previously shown that Aβ25-35 induces oxidative damage to mitochondrial DNA (mtDNA) and that this modality of injury is prevented by melatonin. Because Aβ25-35 does not occur in AD and because the mode of toxicity by Aβ25-35 may be different from that of Aβ1-42 (the physiologically relevant form of Aβ), we extended our initial observations to determine whether oxidative damage to mtDNA could also be induced by Aβ1-42 and whether this type of injury is prevented by melatonin. Exposure of human neuroblastoma cells to Aβ1-42 resulted in marked oxidative damage to mtDNA as determined by a quantitative polymerase chain reaction method. Addition of melatonin to cell cultures along with Aβ completely prevented the damage. This study supports previous findings with Aβ25-35, including a causative role for Aβ in the mitochondrial oxidative lesions present in AD brains. Most important, the data confirms the neuroprotective role of melatonin in Aβ-mediated oxidative injury. Because melatonin also inhibits amyloid aggregation, lacks toxicity, and efficiently crosses the blood-brain barrier, this hormone appears superior to other available antioxidants as a candidate for pharmacologic intervention in AD.

Original languageEnglish (US)
Pages (from-to)226-229
Number of pages4
JournalJournal of Pineal Research
Volume27
Issue number4
DOIs
StatePublished - 1999
Externally publishedYes

Fingerprint

Melatonin
Mitochondrial DNA
Alzheimer Disease
Proteins
Amyloid beta-Peptides
Wounds and Injuries
Staphylococcal Protein A
Blood-Brain Barrier
Neuroblastoma
Amyloid
DNA Damage
Free Radicals
Homeostasis
Cell Culture Techniques
Antioxidants
Hormones
Amino Acids
Polymerase Chain Reaction
Peptides
Brain

Keywords

  • Alzheimer
  • Amyloid
  • DNA
  • Melatonin
  • Mitochondria
  • Oxidative stress

ASJC Scopus subject areas

  • Endocrinology

Cite this

Alzheimer β protein mediated oxidative damage of mitochondrial DNA : Prevention by melatonin. / Pappolla, Miguel; Chyan, Y. J.; Poeggeler, B.; Bozner, P.; Ghiso, J.; LeDoux, S. P.; Wilson, G. L.

In: Journal of Pineal Research, Vol. 27, No. 4, 1999, p. 226-229.

Research output: Contribution to journalArticle

Pappolla, Miguel ; Chyan, Y. J. ; Poeggeler, B. ; Bozner, P. ; Ghiso, J. ; LeDoux, S. P. ; Wilson, G. L. / Alzheimer β protein mediated oxidative damage of mitochondrial DNA : Prevention by melatonin. In: Journal of Pineal Research. 1999 ; Vol. 27, No. 4. pp. 226-229.
@article{93e23d20079b4318a086a95a859dd500,
title = "Alzheimer β protein mediated oxidative damage of mitochondrial DNA: Prevention by melatonin",
abstract = "Most contemporary progress in Alzheimer's disease (AD) stems from the study of a 42-43 amino acid peptide, called the amyloid beta protein (Aβ), as the main neuropathologic marker of the disorder. It has been demonstrated that Aβ has neurotoxic properties and that such effects are mediated by free-radicals. Exposure of neuronal cells to Aβ results in a spectrum of oxidative lesions that are profoundly harmful to neuronal homeostasis. We had previously shown that Aβ25-35 induces oxidative damage to mitochondrial DNA (mtDNA) and that this modality of injury is prevented by melatonin. Because Aβ25-35 does not occur in AD and because the mode of toxicity by Aβ25-35 may be different from that of Aβ1-42 (the physiologically relevant form of Aβ), we extended our initial observations to determine whether oxidative damage to mtDNA could also be induced by Aβ1-42 and whether this type of injury is prevented by melatonin. Exposure of human neuroblastoma cells to Aβ1-42 resulted in marked oxidative damage to mtDNA as determined by a quantitative polymerase chain reaction method. Addition of melatonin to cell cultures along with Aβ completely prevented the damage. This study supports previous findings with Aβ25-35, including a causative role for Aβ in the mitochondrial oxidative lesions present in AD brains. Most important, the data confirms the neuroprotective role of melatonin in Aβ-mediated oxidative injury. Because melatonin also inhibits amyloid aggregation, lacks toxicity, and efficiently crosses the blood-brain barrier, this hormone appears superior to other available antioxidants as a candidate for pharmacologic intervention in AD.",
keywords = "Alzheimer, Amyloid, DNA, Melatonin, Mitochondria, Oxidative stress",
author = "Miguel Pappolla and Chyan, {Y. J.} and B. Poeggeler and P. Bozner and J. Ghiso and LeDoux, {S. P.} and Wilson, {G. L.}",
year = "1999",
doi = "10.1111/j.1600-079X.1999.tb00619.x",
language = "English (US)",
volume = "27",
pages = "226--229",
journal = "Journal of Pineal Research",
issn = "0742-3098",
publisher = "Wiley-Blackwell",
number = "4",

}

TY - JOUR

T1 - Alzheimer β protein mediated oxidative damage of mitochondrial DNA

T2 - Prevention by melatonin

AU - Pappolla, Miguel

AU - Chyan, Y. J.

AU - Poeggeler, B.

AU - Bozner, P.

AU - Ghiso, J.

AU - LeDoux, S. P.

AU - Wilson, G. L.

PY - 1999

Y1 - 1999

N2 - Most contemporary progress in Alzheimer's disease (AD) stems from the study of a 42-43 amino acid peptide, called the amyloid beta protein (Aβ), as the main neuropathologic marker of the disorder. It has been demonstrated that Aβ has neurotoxic properties and that such effects are mediated by free-radicals. Exposure of neuronal cells to Aβ results in a spectrum of oxidative lesions that are profoundly harmful to neuronal homeostasis. We had previously shown that Aβ25-35 induces oxidative damage to mitochondrial DNA (mtDNA) and that this modality of injury is prevented by melatonin. Because Aβ25-35 does not occur in AD and because the mode of toxicity by Aβ25-35 may be different from that of Aβ1-42 (the physiologically relevant form of Aβ), we extended our initial observations to determine whether oxidative damage to mtDNA could also be induced by Aβ1-42 and whether this type of injury is prevented by melatonin. Exposure of human neuroblastoma cells to Aβ1-42 resulted in marked oxidative damage to mtDNA as determined by a quantitative polymerase chain reaction method. Addition of melatonin to cell cultures along with Aβ completely prevented the damage. This study supports previous findings with Aβ25-35, including a causative role for Aβ in the mitochondrial oxidative lesions present in AD brains. Most important, the data confirms the neuroprotective role of melatonin in Aβ-mediated oxidative injury. Because melatonin also inhibits amyloid aggregation, lacks toxicity, and efficiently crosses the blood-brain barrier, this hormone appears superior to other available antioxidants as a candidate for pharmacologic intervention in AD.

AB - Most contemporary progress in Alzheimer's disease (AD) stems from the study of a 42-43 amino acid peptide, called the amyloid beta protein (Aβ), as the main neuropathologic marker of the disorder. It has been demonstrated that Aβ has neurotoxic properties and that such effects are mediated by free-radicals. Exposure of neuronal cells to Aβ results in a spectrum of oxidative lesions that are profoundly harmful to neuronal homeostasis. We had previously shown that Aβ25-35 induces oxidative damage to mitochondrial DNA (mtDNA) and that this modality of injury is prevented by melatonin. Because Aβ25-35 does not occur in AD and because the mode of toxicity by Aβ25-35 may be different from that of Aβ1-42 (the physiologically relevant form of Aβ), we extended our initial observations to determine whether oxidative damage to mtDNA could also be induced by Aβ1-42 and whether this type of injury is prevented by melatonin. Exposure of human neuroblastoma cells to Aβ1-42 resulted in marked oxidative damage to mtDNA as determined by a quantitative polymerase chain reaction method. Addition of melatonin to cell cultures along with Aβ completely prevented the damage. This study supports previous findings with Aβ25-35, including a causative role for Aβ in the mitochondrial oxidative lesions present in AD brains. Most important, the data confirms the neuroprotective role of melatonin in Aβ-mediated oxidative injury. Because melatonin also inhibits amyloid aggregation, lacks toxicity, and efficiently crosses the blood-brain barrier, this hormone appears superior to other available antioxidants as a candidate for pharmacologic intervention in AD.

KW - Alzheimer

KW - Amyloid

KW - DNA

KW - Melatonin

KW - Mitochondria

KW - Oxidative stress

UR - http://www.scopus.com/inward/record.url?scp=0032698216&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032698216&partnerID=8YFLogxK

U2 - 10.1111/j.1600-079X.1999.tb00619.x

DO - 10.1111/j.1600-079X.1999.tb00619.x

M3 - Article

VL - 27

SP - 226

EP - 229

JO - Journal of Pineal Research

JF - Journal of Pineal Research

SN - 0742-3098

IS - 4

ER -