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Review
. 2023 Feb 13;12(4):601.
doi: 10.3390/cells12040601.

Myelinating Glia: Potential Therapeutic Targets in Polyglutamine Spinocerebellar Ataxias

Alexandra F Putka  1   2 , Juan P Mato  1   2 , Hayley S McLoughlin  1
Affiliations
Review

Myelinating Glia: Potential Therapeutic Targets in Polyglutamine Spinocerebellar Ataxias

Alexandra F Putka et al. Cells. .

Abstract

Human studies, in combination with animal and cellular models, support glial cells as both major contributors to neurodegenerative diseases and promising therapeutic targets. Among glial cells, oligodendrocytes and Schwann cells are the myelinating glial cells of the central and peripheral nervous system, respectively. In this review, we discuss the contributions of these central and peripheral myelinating glia to the pathomechanisms of polyglutamine (polyQ) spinocerebellar ataxia (SCA) types 1, 2, 3, 6, 7, and 17. First, we highlight the function of oligodendrocytes in healthy conditions and how they are disrupted in polyQ SCA patients and diseased model systems. We then cover the role of Schwann cells in peripheral nerve function and repair as well as their possible role in peripheral neuropathy in polyQ SCAs. Finally, we discuss potential polyQ SCA therapeutic interventions in myelinating glial.

Keywords: Schwann cell; neurodegeneration; oligodendrocyte; peripheral neuropathy; white matter.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Evidence for white matter and oligodendrocyte abnormalities in polyQ SCA literature. (A) There is direct evidence for a perturbation of oligodendrocyte maturation in SCA1 and 3, with an increase in oligodendrocyte progenitor cells (OPCs)/immature oligodendrocytes and a decrease in mature, myelinating oligodendrocytes in disease. (B) Diffusion tensor imaging and magnetic resonance spectroscopy studies demonstrate alterations to distinct white matter tracts in SCA1, 2, 3, and 6 patients. (C) Mouse models of SCA1, 2, 3, and 17 also support regional white matter alterations or oligodendrocyte involvement in these diseases. Figure created using BioRender.
Figure 2
Figure 2
Evidence for peripheral neuropathy and Schwann cell involvement in polyQ SCA literature. (A) Schematic of Schwann cell maturation. (B) SCA1, 2, 3, and 6 patients are known to present with chronic pain related to peripheral sensory neuropathy as well as reductions in compound muscle action potentials and sensory nerve action potentials that relate to peripheral motor neuropathy. (C) Mouse studies assessing features of polyQ SCA disease-related peripheral neuropathy report axonal degeneration, myelin decompaction, and decreased sensory nerve action potential (SNAP) and compound muscle action potentials (CMAP) amplitudes in peripheral nerves, most noticeably in SCA1, 3, and 7. Figure created using BioRender.
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