Journal Article

DZNE-2021-01426

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Deficiency in MT5-MMP Supports Branching of Human iPSCs-Derived Neurons and Reduces Expression of GLAST/S100 in iPSCs-Derived Astrocytes.

Arnst, N.-I. (First author)DZNE* ; Belio Mairal, P. M.DZNE* ; García-González, L. ; Arnaud, L. ; Greetham, L. ; Nivet, E. ; Rivera, S. ; Dityatev, A. (Last author)DZNE*

2021
MDPI Basel

This record in other databases:    

Please use a persistent id in citations: doi:10.3390/cells10071705

Abstract: For some time, it has been accepted that the β-site APP cleaving enzyme 1 (BACE1) and the γ-secretase are two main players in the amyloidogenic processing of the β-amyloid precursor protein (APP). Recently, the membrane-type 5 matrix metalloproteinase (MT5-MMP/MMP-24), mainly expressed in the nervous system, has been highlighted as a new key player in APP-processing, able to stimulate amyloidogenesis and also to generate a neurotoxic APP derivative. In addition, the loss of MT5-MMP has been demonstrated to abrogate pathological hallmarks in a mouse model of Alzheimer's disease (AD), thus shedding light on MT5-MMP as an attractive new therapeutic target. However, a more comprehensive analysis of the role of MT5-MMP is necessary to evaluate how its targeting affects neurons and glia in pathological and physiological situations. In this study, leveraging on CRISPR-Cas9 genome editing strategy, we established cultures of human-induced pluripotent stem cells (hiPSC)-derived neurons and astrocytes to investigate the impact of MT5-MMP deficiency on their phenotypes. We found that MT5-MMP-deficient neurons exhibited an increased number of primary and secondary neurites, as compared to isogenic hiPSC-derived neurons. Moreover, MT5-MMP-deficient astrocytes displayed higher surface area and volume compared to control astrocytes. The MT5-MMP-deficient astrocytes also exhibited decreased GLAST and S100β expression. These findings provide novel insights into the physiological role of MT5-MMP in human neurons and astrocytes, suggesting that therapeutic strategies targeting MT5-MMP should be controlled for potential side effects on astrocytic physiology and neuronal morphology.

Keyword(s): Action Potentials: physiology (MeSH) ; Amyloid beta-Protein Precursor: genetics (MeSH) ; Amyloid beta-Protein Precursor: metabolism (MeSH) ; Astrocytes: cytology (MeSH) ; Astrocytes: metabolism (MeSH) ; CRISPR-Cas Systems (MeSH) ; Cell Differentiation (MeSH) ; Cell Line (MeSH) ; Excitatory Amino Acid Transporter 1: genetics (MeSH) ; Excitatory Amino Acid Transporter 1: metabolism (MeSH) ; Gene Editing (MeSH) ; Gene Expression Regulation (MeSH) ; Gene Knockout Techniques (MeSH) ; Humans (MeSH) ; Induced Pluripotent Stem Cells: cytology (MeSH) ; Induced Pluripotent Stem Cells: metabolism (MeSH) ; Matrix Metalloproteinases, Membrane-Associated: deficiency (MeSH) ; Matrix Metalloproteinases, Membrane-Associated: genetics (MeSH) ; Neural Stem Cells: cytology (MeSH) ; Neural Stem Cells: metabolism (MeSH) ; Neurons: cytology (MeSH) ; Neurons: metabolism (MeSH) ; Patch-Clamp Techniques (MeSH) ; S100 Calcium Binding Protein beta Subunit: genetics (MeSH) ; S100 Calcium Binding Protein beta Subunit: metabolism (MeSH) ; Signal Transduction (MeSH) ; Alzheimer’s disease ; disease modeling ; hiPSC-derived astrocytes ; human-induced pluripotent stem cells ; metalloproteinase ; morphometry ; neuronal differentiation ; whole-cell patch-clamp ; APP protein, human ; Amyloid beta-Protein Precursor ; Excitatory Amino Acid Transporter 1 ; S100 Calcium Binding Protein beta Subunit ; SLC1A3 protein, human ; MMP24 protein, human ; Matrix Metalloproteinases, Membrane-Associated

Note: CC BY

---

Contributing Institute(s):

1. Molecular Neuroplasticity (AG Dityatev)

Research Program(s):

1. 351 - Brain Function (POF4-351) (POF4-351)

Appears in the scientific report 2021

---

Database coverage:
; ; ; ; Article Processing Charges ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; DOAJ Seal ; Ebsco Academic Search ; Essential Science Indicators ; Fees ; IF >= 5 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

---

---

Linked articles:

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Dataset Dityatev, A.DZNE*
Dataset: Data and statistical analysis for research article on Deficiency in MT5-MMP Supports Branching of Human iPSCs-Derived Neurons and Reduces Expression of GLAST/S100 in iPSCs-Derived Astrocytes published in Cells by Arnst et al. (2021), v1
Mendeley (2021) [10.17632/bfj8pnxfh8.1]2021 BibTeX | EndNote: XML, Text | RIS

---