Nav: Home

Schwann cells 'dine in' to clear myelin from injured nerves

July 06, 2015

Researchers reveal how cells in the peripheral nervous system (PNS) degrade myelin after nerve injury, a process that fails to occur in the central nervous system (CNS). The study appears in The Journal of Cell Biology.

Unlike the CNS, the PNS is capable of significant repair. One reason for this is that Schwann cells, which supply the protective sheath of myelin that covers axons in the PNS, are able to help clear away damaged myelin and guide regeneration after nerve injury. In contrast, the myelin-forming cells in the brain and spinal cord, oligodendrocytes, lack these properties, which helps explains why the CNS has such a limited ability to fix damaged nerves.

The cellular mechanism that enables Schwann cells to break down their own myelin is unclear. This process is key to understanding and treating diseases resulting in myelin damage (demyelination), which can be caused by inherited mutations, illness, age, or injuries.

Researchers previously thought that demyelination by Schwann cells might occur through phagocytosis, whereby the cells gobble up extracellular myelin. But a new study, led by Ashwin Woodhoo (CIC bioGUNE-CIBERehd & Ikerbasque, Spain) and Kristján Jessen (University College London), shows otherwise.

Although Schwann cells and immune cells may employ phagocytosis later in the cleanup process, the new findings indicate that in the first 5-7 days after injury, when 40-50% of the myelin is cleared, Schwann cells digest myelin internally. This cleanup appears to take place through autophagy, with myelin debris inside of Schwann cells being carried to lysosomes in a process the authors term "myelinophagy."

Using mouse sciatic nerves, which are part of the PNS, the researchers found that expression of several autophagy-related genes was induced after injury. Four to seven days after injury, they also observed an abundance of autophagosomes--which deliver cargo to lysosomes for degradation--compared with uninjured nerves, and these autophagosomes contained myelin debris. Inhibiting autophagy led to a notable reduction in myelin breakdown.

The authors also studied mutant mice lacking autophagy function. Although the mutants survived normally and their peripheral nerves were indistinguishable from control mice, they displayed a significant reduction in myelin breakdown after injury compared with the control group. Using a mouse model of Charcot-Marie-Tooth disease, the most common hereditary demyelinating disease, they observed elevated levels of autophagy compared with healthy nerves.

Because myelin breakdown in the CNS is ineffective, the researchers also examined an injured optic nerve. Key indicators of autophagy were not elevated in the optic nerve in contrast to the sciatic, suggesting that the failure of the CNS to clear myelin is associated with reduced activation of autophagy.

"Overall, the findings indicate that autophagy is a mechanism for myelin breakdown in Schwann cells and could provide new targets for manipulating demyelination in injury and disease," says Jessen. "The results also shed new light on the remarkable absence of myelin breakdown in the CNS."

"Further studies are needed to determine if modulating myelinophagy can prevent myelin breakdown in demyelinating diseases or improve nerve repair after PNS and CNS injury," says Woodhoo.
-end-
Gomez-Sanchez, J.A., et al. 2015. J. Cell Biol. doi:10.1083/jcb.201503019

About The Journal of Cell Biology

The Journal of Cell Biology (JCB) is published by The Rockefeller University Press. All editorial decisions on manuscripts submitted are made by leading, research-active scientists in conjunction with our in-house scientific editors. JCB content is posted to PubMed Central, where it is available to the public for free six months after publication. Authors retain copyright of their published works, and third parties may reuse the content for noncommercial purposes under a creative commons license. For more information, please visit http://www.jcb.org.

Rockefeller University Press

Related Autophagy Articles:

Scientists describe a function for autophagy in germline stem-cell proliferation
Scientists study the germline of the roundworm Caenorhabditis elegans to identify the mechanisms that control stem cell proliferation and homeostasis, as well as to advance our molecular understanding of homologous signaling pathways in humans.
New insights on how pathogens escape the immune system
The bacterium Salmonella enterica causes gastroenteritis in humans and is one of the leading causes of food-borne infectious diseases.
Study reveals PGK1 enzyme as therapeutic target for deadliest brain cancer
Discovery of a dual role played by the enzyme phosphoglycerate kinase 1 (PGK1) may indicate a new therapeutic target for glioblastoma, an often fatal form of brain cancer, according to researchers at The University of Texas MD Anderson Cancer Center.
Identification of autophagy-dependent secretion machinery
A group of researchers identified a molecular machinery by which autophagy*1 mediates secretion.
Role for autophagic cellular degradation process in maintaining genomic stability
Tokyo Medical and Dental University-led researchers identified a role for the cellular degradation process autophagy in controlling centrosome number and ensuring genomic stability.
Study suggests that autophagy inhibitors could improve efficacy of chemotherapies
This week in the JCI, research led by Jayanta Debnath at UCSF has shown that inhibiting autophagy does not impair the immune response to tumors during chemotherapy, providing support for the idea that combining autophagy inhibitors with certain chemotherapies may aid cancer treatment.
Taking out the cellular 'trash' - at the right place and the right time
New insight about how cells dispose of their waste is now given by the group of Claudine Kraft at the Max F.
CNIO scientists have discovered a specific molecular biomarker for malignant melanoma
Melanoma is one of the types of cancer that poses the greatest challenge to researchers because it manifests itself in many ways, it contains a large number of mutations and displays high metastatic capacity.
Autophagy under the microscope as never before
We don't tend to wrap our recycling waste in bubble wrap but that's essentially what cells do during the cellular recycling process called autophagy.
Heart bypass without surgery? -- AGGF1 induces therapeutic angiogenesis through autophagy
Coronary artery disease, the number one killer world-wide, restricts and ultimately blocks blood vessels, cutting off oxygen supply to the heart.

Related Autophagy Reading:

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Climate Crisis
There's no greater threat to humanity than climate change. What can we do to stop the worst consequences? This hour, TED speakers explore how we can save our planet and whether we can do it in time. Guests include climate activist Greta Thunberg, chemical engineer Jennifer Wilcox, research scientist Sean Davis, food innovator Bruce Friedrich, and psychologist Per Espen Stoknes.
Now Playing: Science for the People

#527 Honey I CRISPR'd the Kids
This week we're coming to you from Awesome Con in Washington, D.C. There, host Bethany Brookshire led a panel of three amazing guests to talk about the promise and perils of CRISPR, and what happens now that CRISPR babies have (maybe?) been born. Featuring science writer Tina Saey, molecular biologist Anne Simon, and bioethicist Alan Regenberg. A Nobel Prize winner argues banning CRISPR babies won’t work Geneticists push for a 5-year global ban on gene-edited babies A CRISPR spin-off causes unintended typos in DNA News of the first gene-edited babies ignited a firestorm The researcher who created CRISPR twins defends...