Time-dependent DNA condensation induced by amyloid -peptide

¹ Changchun Institute of Applied Chemistry, Graduate School of the Chinese Academy of Sciences
² Changchun Institute of Applied Chemistry

^* To whom correspondence should be addressed. E-mail: xqu{at}ciac.jl.cn.

Submitted on July 17, 2006
Revised on August 21, 2006
Accepted on 14 September 2006

	Abstract

The major protein component of the amyloid deposition in Alzheimer's disease (AD) is a 39-43 residue peptide, amyloid (A). A is toxic to neurons, although the mechanism of neurodegeneration is uncertain. Evidence exists for non-B DNA conformation in the hippocampus of AD brains, and A was reportedly able to transform DNA conformation in vitro. In the present study, we found that DNA conformation was altered in the presence of A, and A induced DNA condensation in a time-dependent manner. Furthermore, A sheets, serving as condensation nuclei, were crucial for DNA condensation, and Cu²⁺ and Zn²⁺ ions inhibited A sheet-induced DNA condensation. Our results suggest DNA condensation as a mechanism of A toxicity.

Key Words: Amyloid beta, DNA, DNA condensation, DNA conformation, circular dichroism, ligand-DNA interaction