First evidence for helical transitions in supercoiled DNA by amyloid β peptide (1-42) and aluminum: A new insight in understanding Alzheimer's disease

Muralidhar Hegde, Suram Anitha, Kallur S. Latha, Mohammed S. Mustak, Reuven Stein, Rivka Ravid, K. S.Jagannatha Rao

Research output: Contribution to journalArticle

66 Scopus citations

Abstract

Previously, we evidenced a B → Z helical change in Alzheimer's brain genomic DNA, leading to a hypothesis that Alzheimer's disease (AD) etiological factors such as aluminum (Al), amyloid β (Aβ) peptide, and Tau might play a role in modulating DNA topology. In the present study, we investigated the interaction of Al and Aβ with DNA. Our results show that Aβ(1-42) could induce a B → ψ (Psi) conformational change in pUC 18 supercoiled DNA (scDNA), Aβ(1-16) caused an altered B-form, whereas Al induced a complex B-C-A mixed conformation. Ethidium bromide binding and agarose gel electrophoresis studies revealed that Al uncoiled the DNA to a fully relaxed form, whereas Aβ(1-42) and Aβ(1-16) effected a partial uncoiling and also showed differential sensitivity toward chloroquine-induced topoisomer separation. Our findings show for the first time that Aβ and Al modulate both helicity and superhelicity in scDNA. A new hypothetical model explaining the potential toxicity of Aβ and Al in terms of their DNA binding properties leading to DNA conformational alteration is proposed.

Original languageEnglish (US)
Pages (from-to)19-31
Number of pages13
JournalJournal of Molecular Neuroscience
Volume22
Issue number1-2
DOIs
StatePublished - Feb 1 2004

Keywords

  • ψ-DNA
  • Alzheimer's disease
  • B-DNA
  • Helical transitions
  • pUC18 supercoiled DNA
  • Topoisomer separation
  • Z-DNA

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry
  • Genetics

Fingerprint Dive into the research topics of 'First evidence for helical transitions in supercoiled DNA by amyloid β peptide (1-42) and aluminum: A new insight in understanding Alzheimer's disease'. Together they form a unique fingerprint.

Cite this