Dimethyl fumarate targets GAPDH and aerobic glycolysis to modulate immunity-Reference-Cited by-同舟云学术

Dimethyl fumarate targets GAPDH and aerobic glycolysis to modulate immunity

Published:2018-04-27 Issue:6387 Volume:360 Page:449-453
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Kornberg Michael D.¹^ORCID,Bhargava Pavan¹^ORCID,Kim Paul M.²,Putluri Vasanta³,Snowman Adele M.⁴,Putluri Nagireddy³⁵,Calabresi Peter A.¹⁴,Snyder Solomon H.²⁴⁶^ORCID

Affiliation:

1. Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.

2. Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.

3. Advanced Technology Core, Baylor College of Medicine, Houston, TX 77030, USA.

4. Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

5. Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.

6. Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

Abstract

Immunometabolism as therapeutic target Dimethyl fumarate (DMF) is an immunomodulatory compound used to treat multiple sclerosis and psoriasis whose mechanisms of action remain only partially understood. Kornberg et al. found that DMF and its metabolite, monomethyl fumarate, succinate the glycolytic enzyme GAPDH (see the Perspective by Matsushita and Pearce). After DMF treatment, GAPDH was inactivated, and aerobic glycolysis was down-regulated in both myeloid and lymphoid cells. This resulted in down-modulated immune responses because inflammatory immune-cell subsets require aerobic glycolysis. Thus, metabolism can serve as a viable therapeutic target in autoimmune disease. Science , this issue p. 449 ; see also p. 377

Funder

National Institutes of Health

American Cancer Society

National Cancer Institute

National Institute of Neurological Disorders and Stroke

Baylor College of Medicine

Cancer Prevention and Research Institute of Texas

U.S. Public Health Service

American Academy of Neurology

National Multiple Sclerosis Society

Race to Erase MS

Publisher