Chitinase 3-like 1 is neurotoxic in multiple sclerosis patient-derived cortical neurons

Abstract

We are pleased to present our latest findings regarding the neurotoxic role of Chitinase 3-like 1 (CHI3L1) in multiple sclerosis (MS). CHI3L1, a 40 kD glycoprotein, is primarily produced by activated astrocytes and microglia in the central nervous system (CNS), and it has garnered considerable attention due to its implications in inflammation and tissue remodelling.1 It is notably increased in several conditions, including MS, and accumulating evidence supports CHI3L1 as a biomarker in early MS, with elevated cerebrospinal fluid (CSF) levels associated with increased disability risk.2, 3 This association led us to investigate whether CHI3L1 simply reflects glial activation or if it exerts direct neurotoxicity. Our prior work in murine neurons demonstrated CHI3L1's neurotoxic effects,4 prompting us to explore its impact on MS patient-derived human induced pluripotent stem cells (hiPSC). Here, we aim to characterize these effects at both molecular and functional levels, further exploring CHI3L1's potential as a biomarker and therapeutic target for MS.