Yuyu Song

Yuyu Song


Start Year: 
2014
Department: 
78 Pearl Street, Apt 2
Institution: 
Yale School of Medicine
Current Institution: 
Yale School of Medicine
Project Title: 

Synaptic Actions of misfolded ALS-associated G85R-SOD1 protein

Abstract: 

Amyotrophic lateral sclerosis (ALS) is a lethal neurodegenerative disease that affects motor neurons and causes progressive muscle weakness, atrophy and paralysis. The best studied subtype of ALS results from mutations in the SOD1 gene (e.g. G85R), whose protein products are misfolded and may cause dysfunction of neuromuscular junctions (NMJ), loss of synapses, “dying-back” degeneration of axons, and neuronal death. Early changes in NMJ suggest an essential role of synaptic dysfunction in ALS pathology. However, the molecular mechanism for the altered synaptic function in ALS is poorly understood, partially due to the lack of a motor neuron system where acute effects can be studied. Using a unique model of squid giant synapse, I will start to answer questions like whetherG85R-SOD1 directly inhibits synaptic transmission, if so, what is the underlying molecular mechanism? Can we prevent or rescue synaptic dysfunction with chaperones? These approaches will help us understand ALS neuropathology, as well as identify potential therapeutic targets for clinical intervention.

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