Amyotrophic lateral sclerosis (ALS) is one of the most devastating neurodegenerative diseases in adults. Patients experience severe weakness and ultimately paralysis when their motor neurons degenerate and die. One example is Stephen Hawking. Scientists thought for a long time how to stop the disease and study the work of the mutant gene, as a result, specially for this, the squid made ALS fall ill. About this writes eNeuro.
To find a cure for ALS, which is fatal, scientists need a deeper understanding of how the disease “interrupts” the communication channels of motor neurons. Since motor neurons extend from the brain to the spinal cord and from the spinal cord to the muscles when they die, the brain can no longer initiate muscle movement.
Therefore, scientists used squid to understand how a mutant protein associated with ALS behaves under controlled conditions. The study clarified the mechanisms underlying nervous dysfunction in ALS and also offers a new approach to restoring the health of motor neurons in patients with the disease.
A mutant protein called G85R-SOD1 has been shown to affect neurotransmission in the squid’s “giant synapse” – the place where neurons transmit chemical signals to muscle fibers, causing the muscles to contract.
The giant squid synapse is one of the few mature nervous systems that mimics human neuromuscular connections, allowing precise experimental manipulations and live measurements.
The presence of an abnormally folded mutant SOD1 gene inhibits synaptic transmission and reduces the pool of synaptic vesicles whose job is to deliver neurotransmitters critical for neuronal connections.
Surprisingly, synaptic function was restored using intermittent high-frequency stimulation, suggesting that aberrant calcium signaling may underlie SOD1 toxicity for normal synaptic transmission.
To test this hypothesis, scientists used calcium imaging to capture abnormal calcium influx in the presynaptic terminal and confirmed the protective role of calcium chelator, which corrected calcium imbalance without affecting neurotransmission.
This suggests a new approach to therapeutic intervention in ALS, in which the chemical or electrical regulation of calcium and its lower signaling pathways can restore the health of motor neurons.