English

The number of patients with age-related neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis (ALS) is steadily increasing in an aging society. In this course, we focus on ALS, which is particularly intractable among these neurodegenerative diseases, and perform research on the pathological molecular mechanism. Based on the results, we aim to develop a new therapy with higher efficacy.

The details are as follows:

1. Analyzing the relationship between function of ALS pathogenic protein TDP-43 and ALS pathology

TDP-43, an RNA-binding protein, is known to mislocalize or abnormally deposit at the lesion site in ALS patients. In ALS, this abnormal function of TDP-43 is assumed to cause various abnormal RNA metabolism, which is involved in the pathology. We focused on the transport of mRNA to neuronal axons, one of the functions of TDP-43, and identified the mRNA of ribosomal proteins as a transport target by TDP-43. This suggests that impaired local protein translation in neuronal axons may be involved in the pathogenesis of ALS. Thus, we are analyzing the molecular mechanism of axonal local translation dysfunction in ALS in more detail using the original axonal analysis method we have established.

Also, we conduct RNA-Seq, splicing analysis, epigenomic analysis, etc. using patient’s nerve tissues to comprehensively understand changes in gene expression including RNA splicing change at lesion sites in ALS patients and identify molecules deeply involved in the pathogenesis of the disease. We plan to apply the seeds obtained from these analyses to the development of a new therapy in the future.