Consequences of Amyloid-β Deficiency for the Liver.

5xFAD TGFβ VEGF eNOS neprilysin presenilin β-secretase 1

Journal

Advanced science (Weinheim, Baden-Wurttemberg, Germany)
ISSN: 2198-3844
Titre abrégé: Adv Sci (Weinh)
Pays: Germany
ID NLM: 101664569

Informations de publication

Date de publication:
02 Mar 2024
Historique:
revised: 27 01 2024
received: 15 10 2023
medline: 3 3 2024
pubmed: 3 3 2024
entrez: 2 3 2024
Statut: aheadofprint

Résumé

The hepatic content of amyloid beta (Aβ) decreases drastically in human and rodent cirrhosis highlighting the importance of understanding the consequences of Aβ deficiency in the liver. This is especially relevant in view of recent advances in anti-Aβ therapies for Alzheimer's disease (AD). Here, it is shown that partial hepatic loss of Aβ in transgenic AD mice immunized with Aβ antibody 3D6 and its absence in amyloid precursor protein (APP) knockout mice (APP-KO), as well as in human liver spheroids with APP knockdown upregulates classical hallmarks of fibrosis, smooth muscle alpha-actin, and collagen type I. Aβ absence in APP-KO and deficiency in immunized mice lead to strong activation of transforming growth factor-β (TGFβ), alpha secretases, NOTCH pathway, inflammation, decreased permeability of liver sinusoids, and epithelial-mesenchymal transition. Inversely, increased systemic and intrahepatic levels of Aβ42 in transgenic AD mice and neprilysin inhibitor LBQ657-treated wild-type mice protect the liver against carbon tetrachloride (CCl

Identifiants

pubmed: 38430535
doi: 10.1002/advs.202307734
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

e2307734

Subventions

Organisme : NIH HHS
ID : 5R01DK128289-03
Pays : United States
Organisme : NIH HHS
ID : 5R01 DK121154-04
Pays : United States
Organisme : NIH HHS
ID : 5P30CA196521-08
Pays : United States

Informations de copyright

© 2024 The Authors. Advanced Science published by Wiley-VCH GmbH.

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Auteurs

Gayane Hrachia Buniatian (GH)

Department of Clinical Pharmacology, University Hospital of Tuebingen, Auf der Morgenstelle 8, 72076, Tuebingen, Germany.

Ute Schwinghammer (U)

Department of Clinical Pharmacology, University Hospital of Tuebingen, Auf der Morgenstelle 8, 72076, Tuebingen, Germany.

Roman Tremmel (R)

Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Auerbachstr. 112, 70376, Stuttgart, Germany.
University of Tuebingen, 72074, Tuebingen, Germany.

Holger Cynis (H)

Department of Drug Design and Target Validation, Fraunhofer Institute for Cell Therapy and Immunology, Weinbergweg 22, 06120, Halle (Saale), Germany.
Junior Research Group, Immunomodulation in Pathophysiological Processes, Faculty of Medicine, Martin-Luther-University Halle-Wittenberg, Weinbergweg 22, 06120, Halle (Saale), Germany.

Thomas S Weiss (TS)

Children's University Hospital (KUNO), University Hospital Regensburg, Franz-Josef-Strauss-Allee 11, 93053, Regensburg, Germany.

Ralf Weiskirchen (R)

Institute of Molecular Pathobiochemistry, Experimental Gene Therapy and Clinical Chemistry, RWTH University Hospital Aachen, Pauwelsstr. 30, 52074, Aachen, Germany.

Volker M Lauschke (VM)

Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Auerbachstr. 112, 70376, Stuttgart, Germany.
University of Tuebingen, 72074, Tuebingen, Germany.
Department of Physiology and Pharmacology Karolinska Institute, Stockholm, 171 77, Sweden.

Sonia Youhanna (S)

Department of Physiology and Pharmacology Karolinska Institute, Stockholm, 171 77, Sweden.

Isbaal Ramos (I)

Innovative Technologies in Biological Systems SL (INNOPROT), Bizkaia, Derio, 48160, Spain.

Maria Valcarcel (M)

Innovative Technologies in Biological Systems SL (INNOPROT), Bizkaia, Derio, 48160, Spain.

Torgom Seferyan (T)

H. Buniatian Institute of Biochemistry, National Academy of Sciences of the Republic of Armenia (NAS RA), 5/1 Paruir Sevak St., Yerevan, 0014, Armenia.

Jens-Ulrich Rahfeld (JU)

Department of Drug Design and Target Validation, Fraunhofer Institute for Cell Therapy and Immunology, Weinbergweg 22, 06120, Halle (Saale), Germany.

Vera Rieckmann (V)

Department of Drug Design and Target Validation, Fraunhofer Institute for Cell Therapy and Immunology, Weinbergweg 22, 06120, Halle (Saale), Germany.

Kathrin Klein (K)

Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Auerbachstr. 112, 70376, Stuttgart, Germany.
University of Tuebingen, 72074, Tuebingen, Germany.

Marine Buadze (M)

Department of Clinical Pharmacology, University Hospital of Tuebingen, Auf der Morgenstelle 8, 72076, Tuebingen, Germany.

Victoria Weber (V)

Department of Clinical Pharmacology, University Hospital of Tuebingen, Auf der Morgenstelle 8, 72076, Tuebingen, Germany.

Valentina Kolak (V)

Department of Clinical Pharmacology, University Hospital of Tuebingen, Auf der Morgenstelle 8, 72076, Tuebingen, Germany.

Rolf Gebhardt (R)

Rudolf-Schönheimer Institute of Biochemistry, Faculty of Medicine, University of Leipzig, Johannisstraße 30, 04103, Leipzig, Germany.

Scott L Friedman (SL)

Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, 1425 Madison Ave, New York, NY, 10029, USA.

Ulrike C Müller (UC)

Institute for Pharmacy and Molecular Biotechnology IPMB, Department of Functional Genomics, University of Heidelberg, Im Neuenheimer Feld 364, 69120, Heidelberg, Germany.

Matthias Schwab (M)

Department of Clinical Pharmacology, University Hospital of Tuebingen, Auf der Morgenstelle 8, 72076, Tuebingen, Germany.
Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Auerbachstr. 112, 70376, Stuttgart, Germany.
Departments of Biochemistry and Clinical Pharmacology, and Neuroscience Laboratory, Yerevan State Medical University, 2- Koryun St, Yerevan, 0025, Armenia.
Cluster of Excellence iFIT (EXC2180) "Image-guided and Functionally Instructed Tumor Therapies", University of Tübingen, 72076, Tübingen, Germany.

Lusine Danielyan (L)

Department of Clinical Pharmacology, University Hospital of Tuebingen, Auf der Morgenstelle 8, 72076, Tuebingen, Germany.
Departments of Biochemistry and Clinical Pharmacology, and Neuroscience Laboratory, Yerevan State Medical University, 2- Koryun St, Yerevan, 0025, Armenia.

Classifications MeSH