THE ESSENTIAL
- Primary cilia are a kind of antennae present on our cells and which have the role of capturing mechanical and biochemical signals.
- The motor neurons of patients with Charcot disease have fewer primary cilia and those that remain are also shorter than normal.
- The researchers discovered that the dysfunction of primary eyelashes is linked to the mutation of the C21orf2 gene.
Dysfunction of primary cilia could be linked to the cause of death of motor neurons and therefore be one of the causes of the development of ALS, or Charcot disease, according to a new study published in the journal Brain. These primary cilia are, according to the National Institute of Health and Medical Research (Inserm), kinds of antennas present on our cells which have the role of capturing mechanical and biochemical signals.
A primary cilia disruption linked to the C21orf2 gene mutation
In previous research, the C21orf2 gene was shown to be linked to Charcot disease. In other pathologies, scientists have already observed that mutations in this gene can disrupt primary eyelashes.
So, in this new study, the researchers wanted to understand if C21orf2 mutations had the same consequences for patients with amyotrophic lateral sclerosis.
The motor neurons of patients with this pathology have fewer primary cilia than those of people who are not diseased. The primary eyelashes that remain are also shorter than normal.
“This structural damage prevents proper signal transmission, indicates Dr Mathias De Decker, first author of the study, in a communiqué. We found (…) that a key pathway for motor neuron health was disrupted. When this happens, motor neurons have difficulty forming essential connections between nerves and muscles, called neuromuscular junctions.”
To see if these consequences on primary cilia were linked to the C21orf2 mutations, the scientists restored C21orf2 levels in the mutated cells. Result: the defects in the cilia were repaired and the signaling pathway as well as the neuromuscular connections were reestablished. They therefore believe that primary cilia could be a therapeutic target for Charcot disease.
Primary cilia, a potential therapeutic target for Charcot disease
In addition to C21orf2, researchers also observed similar cilia defects in the motor neurons of ALS patients with mutations in the ALS and C9orf72 genes. “These observations raise numerous questions and open up prospects for further research.”, estimates Professor Philip Van Damme, another author of the study. Primary cilia could therefore be a very interesting therapeutic target for ALS.
Each year, there are around 2.7 new cases of Charcot disease per 100,000 inhabitants in France, according to Civil hospices of Lyon. This pathology is characterized by progressive paralysis with a fatal outcome.after 3 to 5 years of development on average“, according to Inserm.
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