2. Academic Validation
  3. Oligodendrocyte-encoded lactate dehydrogenase A couples glycolysis to remyelination via protein lactylation

Oligodendrocyte-encoded lactate dehydrogenase A couples glycolysis to remyelination via protein lactylation

  • Neuron. 2026 Mar 16:S0896-6273(26)00137-6. doi: 10.1016/j.neuron.2026.02.032.
Ming-Yue Bao 1,  Xiu-Qing Li 1,  Qing-Qing Sun 1,  Yan He 1,  Yu-Jing Yin 1,  Si-Han Li 1,  Ruo-Yan Du 1,  Gai-Xin Ma 1,  Chen-Yu Feng 1,  Bing Han 1,  Rui Jia 1,  Xuan Wang 2,  Li-Bin Wang 3,  Ya-Ping Yan 4,  Xing Li 5,  Yuan Zhang 6
Affiliations

Affiliations

  • 1 Key Laboratory of Medicinal Resources and Natural Pharmaceutical Chemistry (Shaanxi Normal University), The Ministry of Education, College of Life Sciences, Shaanxi Normal University, Xi'an, Shaanxi 710119, China.
  • 2 Department of Neurology, Fourth Military Medical University, Xijing Hospital, Xi'an, Shaanxi 710119, China.
  • 3 Department of Medical Experimental Center, Shenzhen Nanshan People's Hospital, Shenzhen, Guangdong 518052, China.
  • 4 Key Laboratory of Medicinal Resources and Natural Pharmaceutical Chemistry (Shaanxi Normal University), The Ministry of Education, College of Life Sciences, Shaanxi Normal University, Xi'an, Shaanxi 710119, China. Electronic address: [email protected].
  • 5 Key Laboratory of Medicinal Resources and Natural Pharmaceutical Chemistry (Shaanxi Normal University), The Ministry of Education, College of Life Sciences, Shaanxi Normal University, Xi'an, Shaanxi 710119, China. Electronic address: [email protected].
  • 6 Key Laboratory of Medicinal Resources and Natural Pharmaceutical Chemistry (Shaanxi Normal University), The Ministry of Education, College of Life Sciences, Shaanxi Normal University, Xi'an, Shaanxi 710119, China. Electronic address: [email protected].
PMID: 41844160 DOI: 10.1016/j.neuron.2026.02.032
Abstract

Myelin injury, a hallmark of several neurological diseases, is highly sensitive to glucose metabolism disruptions. Here, we reveal that oligodendrocytes (OLs) within demyelinating lesions exhibit reduced glycolytic efficiency and lactate production compared with mature OLs. Administration of lactate, the product of glycolysis, or specific overexpression of Lactate Dehydrogenase A (LDHA), the enzyme in lactate production, in Olig1+ OLs significantly enhances remyelination. In contrast, conditional knockout of LDHA in the Olig1+ lineage or CNPase+ premyelinating OLs leads to severe neuropathy with dysmyelination in a development-dependent and cell-specific manner. Mechanistic insights show that OLs within demyelinating lesions undergo lactylation silencing, a lactate-induced epigenetic modification that impedes myelin restoration. Furthermore, lactylation of LDHA and Carbonic Anhydrase II (CAII) couples glycolysis with OL maturation. Our findings elucidate the metabolic interplay among glycolysis, lactylation, and OL maturation and provide novel enzymatic therapeutic perspectives for demyelinating disorders, for which effective therapies are currently lacking.

Keywords

demyelinating disease; glycolysis; lactylation; oligodendrocyte; remyelination.

Figures
Products