Molecular mechanisms and sites of action of the gelatinases in autoimmune CNS inflammation: do MMP-2/-9 contribute to meningeal inflammation and secondary cortical damage? (B03)

• Subject Area: Clinical Neurology; Neurosurgery and Neuroradiology
• Term: from 2012 to 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 213904703

Meningeal inflammation results in cortical damage and correlates with disability in MS, but is poorly understood. We showed that gelatinases (matrix metalloproteinase (MMP)-2 and -9) control leukocyte penetration of the blood-brain barrier at postcapillary venules and propose that they serve similar functions at the meningeal-brain border. We will investigate gelatinases in the meninges of MS patients and mouse EAE, identify novel gelatinase substrates that induce meningeal inflammation, and test these substrates in patients. Meningeal T cells will be tracked in mice lacking MMP-2/-9. By understanding meningeal inflammation, we aim to understand drivers of disability in MS.

• DFG Programme: CRC/Transregios
• Subproject of: TRR 128: Initiating/Effector versus Regulatory Mechanisms in Multiple Sclerosis - Progress towards Tackling the Disease
• Applicant Institution: Universität Münster
• Project Heads: Privatdozent Dr. Gerd Meyer zu Hörste, since 1/2021; Professor Dr. Michael Schäfers, until 12/2020; Professorin Dr. Lydia Sorokin