Researchers here outline what is possibly a new point of intervention in the processes that maintain the myelin sheath that wraps nerves. This sheath is vital to the correct operation of the nervous system, and as a consequence demyelinating conditions such as multiple sclerosis are unpleasant and fatal. Loss of myelin isn't just restricted to named conditions, however: some degree of degradation occurs over the course of aging, and is thought to contribute to the progression of cognitive decline. Thus therapies that can boost myelin maintenance may be of greater interest than it might at first appear.
Myelin is maintained by oligodendrocyte cells, and the slow disruption of this cell population and its maintenance activities is the major cause of issues in aging. All cell populations exhibit loss of effectiveness or pathological behavior with the rising levels of inflammation and molecular damage present in older individuals. This research suggests a novel way to attempt to override the cellular reactions to the damage of aging in order to generate more oligodendrocytes and put them back to work. You might compare it with previous efforts that have focused on delivering greater numbers of oligodendrocytes in other ways.
Researchers have found that activation of a specific transcription factor induces in adult stem cells a phenomenon called pathological quiescence. This is when adult stem cells are rendered incapable of responding to injury by producing myelin-forming oligodendrocytes. The failure to remyelinate is the key feature of multiple sclerosis (MS). The work defines the role of the previously undescribed transcription factor known as PRRX1 in human oligodendrocyte progenitor cells, the cells that generate myelin-forming oligodendrocytes.
Current MS research focuses largely on drugs that induce the differentiation of human oligodendrocyte progenitors. In contrast, the UB research presents a novel concept for the development of new drugs based on blocking the pathological quiescence of progenitors. The research demonstrated that PRRX1 expression results in the cell cycle arrest and quiescence of oligodendrocyte progenitors, which disabled the production of myelin. In an animal model of leukodystrophy, the group of genetic disorders in which myelin fails to form or is destroyed, pathological quiescence induced by PRRX1 prevented cell colonization of white matter and effective myelin regeneration by transplanted human oligodendrocyte progenitors.
The researchers also found that blocking expression of this transcription factor prevented the negative effects of proinflammatory cytokines, such as interferon-γ, which regulates its expression. "Blockade of PRRX1 expression prevents the negative effects of interferon-γ, suggesting that PRRX1 expression might be a viable target in inflammatory diseases, such as multiple sclerosis, where interferon-γ may prevent successful myelin regeneration."