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The Beneficial Effect of Mitochondrial Transfer Therapy in 5XFAD Mice via Liver-Serum-Brain Response.
Sweetat, Sahar; Nitzan, Keren; Suissa, Nir; Haimovich, Yael; Lichtenstein, Michal; Zabit, Samar; Benhamron, Sandrine; Akarieh, Karameh; Mishra, Kumudesh; Barasch, Dinorah; Saada, Ann; Ziv, Tamar; Kakhlon, Or; Lorberboum-Galski, Haya; Rosenmann, Hanna.
Afiliación
  • Sweetat S; Department of Neurology, The Agnes Ginges Center for Human Neurogenetics, Hadassah Hebrew University Medical Center, Jerusalem 9112001, Israel.
  • Nitzan K; Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem 9112102, Israel.
  • Suissa N; Department of Neurology, The Agnes Ginges Center for Human Neurogenetics, Hadassah Hebrew University Medical Center, Jerusalem 9112001, Israel.
  • Haimovich Y; Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem 9112102, Israel.
  • Lichtenstein M; Department of Neurology, The Agnes Ginges Center for Human Neurogenetics, Hadassah Hebrew University Medical Center, Jerusalem 9112001, Israel.
  • Zabit S; Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem 9112102, Israel.
  • Benhamron S; The Smoler Protein Research Center, Technion Israel Institute of Technology, Haifa 3200003, Israel.
  • Akarieh K; Department of Biochemistry and Molecular Biology, Institute for Medical Research Israel-Canada (IMRIC), Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem 9112102, Israel.
  • Mishra K; Department of Biochemistry and Molecular Biology, Institute for Medical Research Israel-Canada (IMRIC), Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem 9112102, Israel.
  • Barasch D; Department of Neurology, The Agnes Ginges Center for Human Neurogenetics, Hadassah Hebrew University Medical Center, Jerusalem 9112001, Israel.
  • Saada A; Department of Neurology, The Agnes Ginges Center for Human Neurogenetics, Hadassah Hebrew University Medical Center, Jerusalem 9112001, Israel.
  • Ziv T; Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem 9112102, Israel.
  • Kakhlon O; Department of Neurology, The Agnes Ginges Center for Human Neurogenetics, Hadassah Hebrew University Medical Center, Jerusalem 9112001, Israel.
  • Lorberboum-Galski H; Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem 9112102, Israel.
  • Rosenmann H; Mass Spectrometry Unit, Institute for Drug Research, School of Pharmacy, Hebrew University of Jerusalem, Jerusalem 9112102, Israel.
Cells ; 12(7)2023 03 24.
Article en En | MEDLINE | ID: mdl-37048079
We recently reported the benefit of the IV transferring of active exogenous mitochondria in a short-term pharmacological AD (Alzheimer's disease) model. We have now explored the efficacy of mitochondrial transfer in 5XFAD transgenic mice, aiming to explore the underlying mechanism by which the IV-injected mitochondria affect the diseased brain. Mitochondrial transfer in 5XFAD ameliorated cognitive impairment, amyloid burden, and mitochondrial dysfunction. Exogenously injected mitochondria were detected in the liver but not in the brain. We detected alterations in brain proteome, implicating synapse-related processes, ubiquitination/proteasome-related processes, phagocytosis, and mitochondria-related factors, which may lead to the amelioration of disease. These changes were accompanied by proteome/metabolome alterations in the liver, including pathways of glucose, glutathione, amino acids, biogenic amines, and sphingolipids. Altered liver metabolites were also detected in the serum of the treated mice, particularly metabolites that are known to affect neurodegenerative processes, such as carnosine, putrescine, C24:1-OH sphingomyelin, and amino acids, which serve as neurotransmitters or their precursors. Our results suggest that the beneficial effect of mitochondrial transfer in the 5XFAD mice is mediated by metabolic signaling from the liver via the serum to the brain, where it induces protective effects. The high efficacy of the mitochondrial transfer may offer a novel AD therapy.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Péptidos beta-Amiloides / Enfermedad de Alzheimer Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Cells Año: 2023 Tipo del documento: Article País de afiliación: Israel Pais de publicación: Suiza
Texto completo
Añadir a Mi BVS
Imprimir
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Péptidos beta-Amiloides / Enfermedad de Alzheimer Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Cells Año: 2023 Tipo del documento: Article País de afiliación: Israel Pais de publicación: Suiza