Demyelinating diseases are any conditions that damage the protective coating on nerve cells, the myelin sheath. Some common demyelinating diseases of the central nervous system include multiple sclerosis, neuromyelitis optica spectrum disorder, transverse myelitis, and more. Now, new research led by the University of Connecticut Health and collaborators reveals a protein called C1QL1 promotes the replacement of the cells that produce myelin. The new insights may lead to the development of new and improved therapies for demyelinating diseases.
The findings are published in the FEBS Journal in an article titled, “C1ql1 expression in oligodendrocyte progenitor cells promotes oligodendrocyte differentiation.”
“Myelinating oligodendrocytes arise from the stepwise differentiation of oligodendrocyte progenitor cells (OPCs),” the researchers wrote. “Approximately 5% of all adult brain cells are OPCs. Why would a mature brain need such a large number of OPCs? New myelination is possibly required for higher-order functions such as cognition and learning. Additionally, this pool of OPCs represents a source of new oligodendrocytes to replace those lost during injury, inflammation, or in diseases such as multiple sclerosis (MS). How OPCs are instructed to differentiate into oligodendrocytes is poorly understood, and for reasons presently unclear, resident pools of OPCs are progressively less utilized in MS. The complement component 1, q subcomponent-like (C1QL) protein family has been studied for their functions at neuron–neuron synapses, but we show that OPCs express C1ql1. We created OPC-specific conditional knockout mice and showed that C1QL1 deficiency reduces the differentiation of OPCs into oligodendrocytes and reduces myelin production during both development and recovery from cuprizone-induced demyelination.”
In experiments conducted in mice, the researchers observed deleting the gene that codes for C1QL1 caused a delay in the rate at which oligodendrocytes (the cells that make myelin) mature, leading to reduced myelination of neurons.
After mice were fed a drug that destroys myelin, recovery of oligodendrocytes and myelination was delayed in mice lacking the C1QL1 protein. Causing mice to express more C1QL1, however, led to increased numbers of oligodendrocytes and more myelination upon drug withdrawal, suggesting that C1QL1 helps restore the damaged myelin layer. Thus, investigational therapies that boost C1QL1 may hold promise against demyelinating diseases.
“Our basic research on C1QL1 is nascent, but there is potential that it is relevant for a novel treatment for multiple sclerosis,” said corresponding author David C. Martinelli, PhD, of the University of Connecticut Health Center. “New drug treatment options for patients with multiple sclerosis could have a large impact on their quality of life.”
