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Volume 8, Issue 6 J Neurol Neurosci
ISSN: 2171-6625 Neuro, an open access journal Neuroscience 2017
October 16-17, 2017
OCTOBER 16-17, 2017 OSAKA, JAPAN
17TH Global Neuroscience Conference
Defining conserved spinal muscular atrophy gene networks that are involved in neuromuscular system
using Drosophila SMA model
Takakazu Yokokura
Okinawa Institute Science and Technology, Japan
Spinal Muscular Atrophy (SMA) is a devastating inherited disorder characterized by progressive loss of motor activity, failure
of neuromuscular synapses and muscle weakness. Genetic cause of SMA is mutation of Survival Motor Neuron 1 (SMN1)
gene, while genetic factor determining severity of symptom is copy number of Survival Motor Neuron 2 (SMN2) gene, which
only generate small amount of SMN protein due to skipping a functionally important exon at high frequency. As SMN has been
considered as a key factor to regulate neuronal cell function cell autonomously, up-regulating SMN protein in spinal cord motor
neurons at pre-symptomatic stages is the most advanced therapeutic approaches to prevent, or, at least, delay irreversible loss of
motor neurons. However, the fact that SMA patients exhibit muscle weakness and experience fatigue suggests that it is little known
underlying mechanism how low SMN levels affect to trans-synaptic biology at the neuromuscular junction (NMJ). Trans-synaptic
structure and signaling at the NMJ play important roles for establishment and maintenance of neuromuscular connectivity
and functions. As pathological observation in post-mortal NMJ specimen or rodent SMA models exhibited abnormality in
neuromuscular connectivity, utilizing Drosophila NMJ, which is well characterize its structure and molecular mechanism, allow
us to understand how low levels of SMN perturbs structure and molecular mechanism at the NMJ in depth. Severe SMN mutants
exhibited two phenotypes in motor unit known as SMA pathology, loss of motor axon and abnormality at the NMJ. Modulation of
trans-synaptic two canonical signaling pathways, BMP and FGF signaling, that have shown genetic interaction to SMN, can rescue
the SMN defects. In addition, each pathway seems to modulate distinct aspect of SMA motor unit pathology.
Biography
Takakazu Yokokura has his expertise in genetics and molecular biology and passion in finding approaches to cure devastated neurological disorders, such as
Spinal Muscular Atrophy (SMA) and amyotrophic lateral sclerosis. His study has focused on elucidate underlying molecular mechanisms that low levels of SMN
leads to manifestation of SMA neuromuscular pathological phenotypes.
Takakazu Yokokura, J Neurol Neurosci 2017, 8:6
DOI: 10.21767/2171-6625-C1-005