

INVITED REVIEW Year : 2017 | Volume : 12 | Issue : 8 | Page : 1262-1267

Metabolic pathways as possible therapeutic targets for progressive multiple sclerosis



Rebecca M Heidker1, Mitchell R Emerson2, Steven M LeVine Ph.D. 1

1 Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, KS, USA

2 Department of Pharmaceutical Sciences, College of Pharmacy-Glendale, Midwestern University, Glendale, AZ, USA



Date of Acceptance 09-Aug-2017 Date of Web Publication 5-Sep-2017

Correspondence Address:

Steven M LeVine

Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, KS

USA

Source of Support: None, Conflict of Interest: RMH is currently employed by Employer Solutions, a division of Quest Diagnostics. SML has received funding from ApoPharma, Inc. Check 5

DOI: 10.4103/1673-5374.213542



Abstract

Unlike relapsing remitting multiple sclerosis, there are very few therapeutic options for patients with progressive forms of multiple sclerosis. While immune mechanisms are key participants in the pathogenesis of relapsing remitting multiple sclerosis, the mechanisms underlying the development of progressive multiple sclerosis are less well understood. Putative mechanisms behind progressive multiple sclerosis have been put forth: insufficient energy production via mitochondrial dysfunction, activated microglia, iron accumulation, oxidative stress, activated astrocytes, Wallerian degeneration, apoptosis, etc. Furthermore, repair processes such as remyelination are incomplete. Experimental therapies that strive to improve metabolism within neurons and glia, e.g., oligodendrocytes, could act to counter inadequate energy supplies and/or support remyelination. Most experimental approaches have been examined as standalone interventions; however, it is apparent that the biochemical steps being targeted are part of larger pathways, which are further intertwined with other metabolic pathways. Thus, the potential benefits of a tested intervention, or of an established therapy, e.g., ocrelizumab, could be undermined by constraints on upstream and/or downstream steps. If correct, then this argues for a more comprehensive, multifaceted approach to therapy. Here we review experimental approaches to support neuronal and glial metabolism, and/or promote remyelination, which may have potential to lessen or delay progressive multiple sclerosis.

Keywords: acetyl-coenzyme A carboxylase; biotin; estrogen; iron; Kynurenine pathway; mitochondria; thyroid hormone; remyelination; stem cells; vitamin D

How to cite this article:

Heidker RM, Emerson MR, LeVine SM. Metabolic pathways as possible therapeutic targets for progressive multiple sclerosis. Neural Regen Res 2017;12:1262-7

How to cite this URL:

Heidker RM, Emerson MR, LeVine SM. Metabolic pathways as possible therapeutic targets for progressive multiple sclerosis. Neural Regen Res [serial online] 2017 [cited 2020 Sep 24];12:1262-7. Available from: http://www.nrronline.org/text.asp?2017/12/8/1262/213542

Introduction

Wallerian degeneration

More Details

Table 1: Potential approaches to support metabolism and/or remyelination for progressive multiple sclerosis



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The Intertwined Roles of Biotin, Iron and Vitamin D for Metabolic Support

Additional Experimental Approaches to Promote Metabolism

Conclusions

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Author contributions: SML conceived and designed the paper. RMH, MRE, and SML all contributed to the writing of the review.

Conflicts of interest: RMH is currently employed by Employer Solutions, a division of Quest Diagnostics. SML has received funding from ApoPharma, Inc.

Plagiarism check: Checked twice by iThenticate.

Peer review: Externally peer reviewed.

Open peer reviewer: Mohammad Khalaj-Kondori, University of Tabriz, Iran.

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