Deciphering the role of lactylation, a novel protein post-translational modification, in ALS (2026-2027)
Abstract
This project seeks to uncover how lactylation, a recently identified post-translational modification regulated by lactate metabolism, contributes to ALS pathology. Our preliminary data reveal that lactylation occurs on key ALS-associated proteins, including TDP-43 and SOD1. We will define lactylation signatures in ALS, determine how this modification influences TDP-43 and SOD1 mislocalisation and aggregation, and assess whether modulating lactylation can confer neuroprotection. These studies will provide new mechanistic insights into ALS and establish whether lactylation represents a viable therapeutic target.
