What are neuromuscular junctions and how do they play a role in the development of Charcot-Marie-Tooth disease (CMT)? According to Charcot-Marie-Tooth News, researchers discovered that structural neuromuscular junction changes caused worsening nerve and muscle degeneration in patients with CMT2D, a subtype of CMT. Check out the full study findings published in Cell Death & Disease.
Neuromuscular Junction
KenHub describes the neuromuscular junction as:
a type of synapse where neuronal signals from the brain or spinal cord interact with skeletal muscle fibers, causing them to contract. The neuromuscular junction then, is a key component in the body’s ability to produce and control movement.
Prior research into mice models of CMT2D highlighted how neuromuscular junction abnormalities often preceded degeneration. This more recent study also utilized mice models of CMT2D. While their main goal was to understand what factors contribute to the degeneration patterns seen with CMT2D, researchers also sought to learn how neuromuscular junction development related to muscle degeneration.
Normally, muscle fibers connect to synapses, a type of neuron. In mice, these multiple connections are replaced within 2 weeks of birth, leaving a single neuron linked to each specific muscle fiber. AChR, a type of receptors which help receive and translate nerve signals, then move to their spot within the neuromuscular junction.
However, this process does not work, is interrupted, or is inhibited in CMT2D. AChRs do not move to their proper placements. This caused weakness, nerve loss, and degeneration that could be seen particularly in the back legs. Researchers determined that, within these mice models, both AChR and synapse issues can cause worsening degeneration. Additionally, more structural changes around nerve branches and other elements created a heightened vulnerability to degeneration.
Charcot-Marie-Tooth Disease (CMT)
Although Charcot-Marie-Tooth disease (CMT) is rare, it is also one of the most commonly inherited neurological disorders. This condition affects the peripheral nerves around the brain and spinal cord. A variety of gene mutations cause CMT. However, the exact CMT subtype is dependent on the specific changes. For example, people with CMT1 and CMT2D do not have the same genetic mutations; CMT2D is caused by a GARS1 variant. Regardless, these gene mutations cause the degeneration of peripheral nerves. CMT is usually diagnosed in adolescence or early adulthood, though symptoms can develop even into mid-adulthood. These symptoms include:
- Instability
- Muscle atrophy in the hands, feet, and lower legs
- Poor coordination
- Muscle weakness
- Frequent tripping
- Food drop
- High arches and hammertoes
- Lowered sensation in the legs
- Muscle contractions
