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A Toxicogenic Interaction between Intracellular Amyloid-ß and Apolipoprotein-E.
Dey, Arpan; Verma, Aditi; Bhaskar, Uchit; Sarkar, Bidyut; Kallianpur, Mamata; Vishvakarma, Vicky; Das, Anand Kant; Garai, Kanchan; Mukherjee, Odity; Ishii, Kunihiko; Tahara, Tahei; Maiti, Sudipta.
Afiliación
  • Dey A; Department of Chemical Sciences, Tata Institute of Fundamental Research, Mumbai 400005, India.
  • Verma A; Department of Chemical Sciences, Tata Institute of Fundamental Research, Mumbai 400005, India.
  • Bhaskar U; Institute of Stem Cell Science and Regenerative Medicine, Bangalore 560065, India.
  • Sarkar B; Molecular Spectroscopy Laboratory, RIKEN, Wako, Saitama 3510198, Japan.
  • Kallianpur M; Department of Chemical Sciences, Tata Institute of Fundamental Research, Mumbai 400005, India.
  • Vishvakarma V; Department of Chemical Sciences, Tata Institute of Fundamental Research, Mumbai 400005, India.
  • Das AK; Department of Chemical Sciences, Tata Institute of Fundamental Research, Mumbai 400005, India.
  • Garai K; Tata Institute of Fundamental Research, Hyderabad 500107, India.
  • Mukherjee O; Institute of Stem Cell Science and Regenerative Medicine, Bangalore 560065, India.
  • Ishii K; Molecular Spectroscopy Laboratory, RIKEN, Wako, Saitama 3510198, Japan.
  • Tahara T; Molecular Spectroscopy Laboratory, RIKEN, Wako, Saitama 3510198, Japan.
  • Maiti S; Department of Chemical Sciences, Tata Institute of Fundamental Research, Mumbai 400005, India.
ACS Chem Neurosci ; 15(6): 1265-1275, 2024 03 20.
Article en En | MEDLINE | ID: mdl-38421952
ABSTRACT
Alzheimer's disease (AD) is associated with the aggregation of amyloid ß (Aß) and tau proteins. Why ApoE variants are significant genetic risk factors remains a major unsolved puzzle in understanding AD, although intracellular interactions with ApoE are suspected to play a role. Here, we show that specific changes in the fluorescence lifetime of fluorescently tagged small Aß oligomers in rat brain cells correlate with the cellular ApoE content. An inhibitor of the Aß-ApoE interaction suppresses these changes and concomitantly reduces Aß toxicity in a dose-dependent manner. Single-molecule techniques show changes both in the conformation and in the stoichiometry of the oligomers. Neural stem cells derived from hiPSCs of Alzheimer's patients also exhibit these fluorescence lifetime changes. We infer that intracellular interaction with ApoE modifies the N-terminus of the Aß oligomers, inducing changes in their stoichiometry, membrane affinity, and toxicity. These changes can be directly imaged in live cells and can potentially be used as a rapid and quantitative cellular assay for AD drug discovery.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Péptidos beta-Amiloides / Enfermedad de Alzheimer Límite: Animals / Humans Idioma: En Revista: ACS Chem Neurosci Año: 2024 Tipo del documento: Article País de afiliación: India Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Péptidos beta-Amiloides / Enfermedad de Alzheimer Límite: Animals / Humans Idioma: En Revista: ACS Chem Neurosci Año: 2024 Tipo del documento: Article País de afiliación: India Pais de publicación: Estados Unidos