Aug 17 2021

A Clue to the Etiology of Demyelinating Diseases

The research group of a graduate student SIMANKOVA Anna, Assistant Professor BIZEN Norihisa and Professor TAKEBAYASHI Hirohide (Division of Neurobiology and Anatomy at the Graduate School of Medical and Dental Sciences of Niigata University) found that Ddx20¹ is an essential factor for the differentiation and maturation of oligodendrocytes² that form myelin surrounding the axons in the brain and spinal cord. This study elucidates a part of the mechanism for myelin formation, which is indispensable for neuronal function and homeostasis, and provides clues to potential therapies for intractable neurological diseases caused by oligodendrocyte abnormalities such as multiple sclerosis. This research was conducted in collaboration by Emeritus Professor SAKIMURA Kenji and Associate Professor ABE Manabu in the Brain Research Institute of Niigata University, Professor SHIBATA Shinsuke in the Graduate School of Medical and Dental Sciences of Niigata University and Professor OHNO Nobuhiko in Jichi Medical University (Visiting Professor of National Institute for Physiological Sciences). The research results were published online on July 7, 2021 in Glia.

Research Results

• Myelin, which is formed by oligodendrocytes around the neuronal axons, plays an important role in facilitating neurotransmission and protecting axons.
• Analysis of Ddx20 gene mutant mice demonstrated that Ddx20 is involved in the differentiation and survival of oligodendrocytes and that it is essential for myelination.
• Ddx20 is essential for RNA splicing, maintenance of myelin-related gene expression, and oligodendrocyte survival.

Glossary

(Note 1) Ddx20 (DEAD box helicase 20):
Ddx20, also known as Gemin3 or DP103, is one of the RNA helicases, which are enzymes that change the RNA structure. Ddx20 binds to SMN, which is encoded by the causative gene for spinal muscular atrophy (SMA), a motor neuron disease. Ddx20 forms SMN complex and regulates RNA metabolism such as RNA splicing. The Ddx family proteins are also known to have multiple roles in the processes of RNA transport, gene expression and protein translation.

(Note 2) Oligodendrocyte:
Oligodendrocyte is one of the glial cells that compose the brain and spinal cord. It is abundant in the white matter region. It forms a sheet-like membrane that wraps around the neuronal axon to form a structure called myelin. Since myelin is rich in lipids and acts as an electrical insulator, it accelerates the conduction velocity of electrical signals transmitted along axons. Myelin also maintains neuronal homeostasis by protecting axons and supporting neuronal metabolism.

Publication Details

Journal: Glia
Title: Ddx20, DEAD box helicase 20, is essential for the differentiation of oligodendrocyte and maintenance of myelin gene expression
Authors: Anna Simankova, Norihisa Bizen, Sei Saitoh, Shinsuke Shibata, Nobuhiko Ohno, Manabu Abe, Kenji Sakimura, Hirohide Takebayashi
DOI: 10.1002/glia.24058