Researchers at Nagoya University in Japan have identified a novel genetic variant found in some patients with Amyotrophic lateral sclerosis (ALS). Employing human-induced pluripotent stem (iPS) cells, they detailed the process by which this variant relates to ALS. The investigators expect this mechanism to be a new therapeutic target for ALS treatment. The findings are reported in the Journal of Neuroscience.
Dr. Satoshi Yokoi and his colleagues in the Department of Neurology, Nagoya University Graduate School of Medicine, have been studying this FUS protein. Previously, they found that the FUS protein interacted with RNA that encodes a protein called SYNGAP1. SYNGAP1 helps with synaptic formation, which is essential for neurons to work together.
Currently, no study has reported that SYNGAP1 is involved in the mechanism of ALS. However, given its close relationship with FUS, we wanted to investigate whether SYNGAP1 has anything to do with ALS.Dr. Yokoi, a lead author of the study.
Excessive binding of HNRNPK to SYNGAP1 was causing synaptic abnormality, which explains the process of early-stage ALS when synapse loss takes place. Additionally, while previous ALS research focused on FUS, this study underscored the crucial roles of SYNGAP1 and HNRNPK. The antisense RNA used in the current research is only effective for those patients with the variant SYNGAP1. Nonetheless, the researchers hope that the discovery of this new mechanism can provide new insight into other types of ALS.
Interestingly, this study also found that SYNGAP1 behaved differently in human iPS cells compared to the mouse model, which had been used for SYNGAP1 research.
We believe that using human-derived samples is crucial so that the observations from these cells directly apply to patients.Dr. Yokoi.
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