|
Dysregulation of the APOE-TGFB pathway leads to loss of the microglial homeostatic signature in neurologic diseases at scelerisque| old_uid | 14607 |
|---|
| title | Dysregulation of the APOE-TGFB pathway leads to loss of the microglial homeostatic signature in neurologic diseases at scelerisque |
|---|
| start_date | 2014/11/07 |
|---|
| schedule | 11h30 |
|---|
| online | no |
|---|
| details | Séminaire FBN. Une invitation d'Agnès Nadjar (NutriNeuro) |
|---|
| summary | Microglia are resident macrophages of the central nervous system (CNS) that participate both in normal CNS function and disease. We identified a unique molecular and functional homeostatic signature in microglia. Based on this signature, we generated novel microglial surface specific antibodies and identified novel targets in resident microglia that can serve as therapeutic targets. We also identified unique patterns of microglia dysfunction associated with CNS disease in animal models of EAE, ALS and AD. We found that the homeostatic microglial signature is dependent on TGFB signaling. In mouse models of MS ALS and AD microglia acquire a cytotoxic phenotype mediated by intrinsic activation of the APOE pathway which suppresses the microglia homeostatic molecular properties and leads to uncontrolled chronic inflammation. Treatments aimed at targeting microglia by suppressing the APOE pathway results in activation of both the TGFB pathway and TAM system (Tyro3, Axl and Mertk) which abrogates the inflammatory microglial phenotype and restores microglial homeostatic properties. In summary, we have identified the APOE-TGFB axis as a critical common regulatory pathway in microglia. This pathway is dysregulated in both inflammatory and degenerative diseases of the CNS. |
|---|
| responsibles | Deris |
|---|
| |
|