Glycolic acid and D-lactate-putative products of DJ-1-restore neurodegeneration in FUS - and SOD1-ALS

Research output: Contribution to journalResearch articleContributedpeer-review



Amyotrophic lateral sclerosis (ALS) leads to death within 2-5 yr. Currently, available drugs only slightly prolong survival. We present novel insights into the pathophysiology of Superoxide Dismutase 1 (SOD1)- and in particular Fused In Sarcoma (FUS)-ALS by revealing a supposedly central role of glycolic acid (GA) and D-lactic acid (DL)-both putative products of the Parkinson's disease associated glyoxylase DJ-1. Combined, not single, treatment with GA/DL restored axonal organelle phenotypes of mitochondria and lysosomes in FUS- and SOD1-ALS patient-derived motoneurons (MNs). This was not only accompanied by restoration of mitochondrial membrane potential but even dependent on it. Despite presenting an axonal transport deficiency as well, TDP43 patient-derived MNs did not share mitochondrial depolarization and did not respond to GA/DL treatment. GA and DL also restored cytoplasmic mislocalization of FUS and FUS recruitment to DNA damage sites, recently reported being upstream of the mitochondrial phenotypes in FUS-ALS. Whereas these data point towards the necessity of individualized (gene-) specific therapy stratification, it also suggests common therapeutic targets across different neurodegenerative diseases characterized by mitochondrial depolarization.


Original languageEnglish
JournalLife science alliance
Issue number8
Publication statusPublished - 1 Aug 2024

External IDs

PubMed 38760174
ORCID /0000-0002-7688-3124/work/161891537



  • Humans, Amyotrophic Lateral Sclerosis/metabolism, RNA-Binding Protein FUS/metabolism, Glycolates/metabolism, Mitochondria/metabolism, Protein Deglycase DJ-1/metabolism, Lactic Acid/metabolism, Superoxide Dismutase-1/metabolism, Membrane Potential, Mitochondrial, Motor Neurons/metabolism, Lysosomes/metabolism