APP‐C31: An Intracellular Promoter of Both Metal‐Free and Metal‐Bound Amyloid‐β40 Aggregation and Toxicity in Alzheimer's Disease
Source abstract
Abstract
Abstract Intracellular C‐terminal cleavage of the amyloid precursor protein (APP) is elevated in the brains of Alzheimer's disease (AD) patients and produces a peptide labeled APP‐C31 that is suspected to be involved in the pathology of AD. But details about the role of APP‐C31 in the development of the disease are not known. Here, this work reports that APP‐C31 directly interacts with the N‐terminal and self‐recognition regions of amyloid‐β40 (Aβ40) to form transient adducts, which facilitates the aggregation of both metal‐free and metal‐bound Aβ40 peptides and aggravates their toxicity. Specifically, APP‐C31 increases the perinuclear and intranuclear generation of large Aβ40 deposits and, consequently, damages the nucleus leading to apoptosis. The Aβ40‐induced degeneration of neurites and inflammation are also intensified by APP‐C31 in human neurons and murine brains. This study demonstrates a new function of APP‐C31 as an intracellular promoter of Aβ40 amyloidogenesis in both metal‐free and metal‐present environments, and may offer an interesting alternative target for developing treatments for AD that have not been considered thus far.
Source: crossref · Quality: baseline
Research context
OpenAlex topics: Alzheimer's disease research and treatments · Trace Elements in Health · Signaling Pathways in Disease
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
Affiliations
Department of Chemistry Korea Advanced Institute of Science and Technology (KAIST) Daejeon 34141 Republic of Korea
Research Center for Bioconvergence Analysis Korea Basic Science Institute (KBSI) Ochang Chungbuk 28119 Republic of Korea
Center for Catalytic Hydrocarbon Functionalizations Institute for Basic Science (IBS) Daejeon 34141 Republic of Korea
Graduate School of Medical Science and Engineering KAIST Daejeon 34141 Republic of Korea
Rare Disease Research Center Korea Research Institute of Bioscience and Biotechnology (KRIBB) Daejeon 34141 Republic of Korea
Department of Biochemistry Department of Medical Science Chungnam National University School of Medicine Daejeon 35015 Republic of Korea
Bio‐Analytical Science University of Science and Technology (UST) Daejeon 34113 Republic of Korea
Graduate School of Analytical Science and Technology Chungnam National University Daejeon 34134 Republic of Korea
Department of Systems Biotechnology Chung‐Ang University Gyeonggi 17546 Republic of Korea
Frontier Research Institute for Interdisciplinary Sciences Tohoku University Miyagi 980‐8578 Japan
Funding
National Research Foundation of Korea · National Research Council of Science and Technology · Korea Basic Science Institute · Institute for Basic Science · Ministry of Education
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