| Title: |
Investigating the role of Clec7a in microglia function and assessing whether it may represent an early molecular target in Alzheimer Disease (AD) |
| Authors: |
Prieur, M.; Hemonnot-Girard, Anne Laure; Provost, Coralie Clua; Phuadraksa, Thanawat; Crozet, C.; Garcia, V.; Linck, N.; Compan, Vincent; Rassendren, F.; E. Hirbec, Hélène |
| Contributors: |
Institut de Génomique Fonctionnelle (IGF); Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM); Institut des Neurosciences de Montpellier (INM); Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM); Network Glia |
| Source: |
XVI European Meeting on Glial Cells in Health and Disease, Berlin, July 8–11, 2023 ; https://hal.science/hal-04731876 ; XVI European Meeting on Glial Cells in Health and Disease, Berlin, July 8–11, 2023, Jul 2023, Berlin, Germany. Wiley, Glia, 71 (S1), pp.T16-141C, 2023 ; https://onlinelibrary.wiley.com/toc/10981136/2023/71/S1 |
| Publisher Information: |
CCSD; Wiley |
| Publication Year: |
2023 |
| Collection: |
Université de Montpellier: HAL |
| Subject Terms: |
[SDV]Life Sciences [q-bio] |
| Subject Geographic: |
Berlin; Germany |
| Description: |
International audience ; Human genetic studies revealed that microglia express many genes that are significant risk factors for Alzheimer Disease (AD), thus supporting key contribution of microglia to the pathogenesis, but also opening new opportunities for therapeutic interventions. Further, longitudinal imaging studies in patients suggested that early microglia reaction could be beneficial for the disease outcome. Yet, the molecular players and the signaling pathways involved in AD early stages remain unknown. We recently demonstrated microglial up-regulation of Clec7a/Dectin-1 at early stages in Ab models of AD. We validated its clinical relevance by highlighting CLEC7A upregulation in the cortex of patients with AD and in microglia derived from AD induced pluripotent stem cells. In peripheral immune cells, Clec7a/Dectin-1 is recognized as a pattern-recognition receptor and was shown to regulate immune-related functions that are highly relevant to AD, i.e. phagocytosis, reactive oxygen species (ROS) production and cytokine release. Importantly, Clec7a/Dectin-1 receptor also shares signaling pathways with other proteins like TREM2 which are acknowledged players in AD pathogenesis. These findings support our hypothesis that Clec7a/Dectin-1 plays a key role in the early phases of the disease and may represent a relevant molecular target in AD early stages. This being said, the microglial functions of Clec7a/Dectin-1 in either physiological or pathological contexts are currently unknown.In the present study, we investigated the role of microglial Dectin-1 by characterizing its impact on microglia cell morphology both in-vitro and in-vivo. We also evaluated its functional roles by measuring the impact of its deletion on phagocytosis, ROS production and cytokines release, both in control and stimulated conditions. Our initial results will pave the way to highlighting to role of Clec7a/Dectin-1 in microglia biology. |
| Document Type: |
conference object; still image |
| Language: |
English |
| Availability: |
https://hal.science/hal-04731876 |
| Accession Number: |
edsbas.E19DC250 |
| Database: |
BASE |