Interactions of amyloid precursor protein intracellular domain (AICD) with copper and DNA fragment reveal conformational changes that trigger AD

Kumar, DJ and Govindaraju, M and Narayan, P and Ramasamy, P and Nagendra, HG and Jagannatha Rao, KS and Easwaran, KRK (2022) Interactions of amyloid precursor protein intracellular domain (AICD) with copper and DNA fragment reveal conformational changes that trigger AD. In: Current Topics in Peptide and Protein Research, 23 . pp. 37-46.

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Abstract

Neurofibrillary tangles and Amyloid plaques are central to the progression of Alzheimer’s disease [AD]. It has been well substantiated that the Amyloid precursor protein is cleaved enzymatically at its C terminal end yielding the APP intracellular domain [AICD]. It has been shown that AICD is an intrinsically unstructured molecule involved in AD pathology and appears to be a potential candidate in understanding the complexity of this disease. However, the relevance of AICD mechanism in neurodegeneration is poorly understood. Recent evidences reveal that AICD is localized in the nucleus, and upon binding to DNA, gene expression appears to get altered, and this could be regarded as the third hallmark of AD. Reports have highlighted that higher concentrations of copper induces a neurotoxic effect, which could enhance the AD pathogenesis. Hence, our work using circular dichroism and computational studies focuses on the interactions of AICD with copper and DNA which indicates that AICD-Cu complex interacts with the DNA and triggers conformational perturbations leading to AD.

Item Type:	Journal Article
Publication:	Current Topics in Peptide and Protein Research
Publisher:	Research Trends (P) LTD.
Additional Information:	The copyright for this article belongs to Research Trends (P) LTD.
Keywords:	AICD; Alzheimer’s disease (AD); circular dichroism; copper; DNA; docking studies
Department/Centre:	Division of Biological Sciences > Molecular Biophysics Unit
Date Deposited:	06 May 2023 03:11
Last Modified:	06 May 2023 03:11
URI:	https://eprints.iisc.ac.in/id/eprint/81280

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