Institute of Biomedical Research and InnovationDepartment of Brain and Neurodegenerative Disease Research

Minako Hoshi

Understanding the brain and developing solutions for Alzheimer’s disease

Department of Brain and Neurodegenerative Disease Research

Minako Hoshi, Ph.D.

Research Overview

Our department is committed to developing treatments for neurodegenerative diseases, in particular Alzheimer’s disease, so that people can live a good and healthy life.

Research focus

~Protecting your brain means protecting your future. ~

Throughout your life, your brain is developing.

For humans, “memory” is not just a “record.” We develop the ability to visualize the future that we want from our memories, to select what is needed to make it happen and to change the neuronal network according to our experiences. This is the essential difference between the brain and a computer. When a person develops Alzheimer's disease, which causes dementia, the neuronal network that has been developed over many years is slowly damaged. Eventually, neurons are completely lost. This disease gradually robs you of who you are and ultimately leaves you unable to do anything for yourself.

We still don't know why a new drug for Alzheimer's disease is effective.

Recently, it has been reported that antibodies against a small protein called amyloid-β protein (Aβ) can ameliorate Alzheimer's disease to some extent, giving us a ray of hope for an effective treatment. Aβ is an important protein that protects neurons in healthy brains, but it has a soft string-like structure that can take various forms. Multiple studies have shown that when Aβ assembles into abnormal shapes, the resulting Aβ assemblies become toxic. There are many forms of Aβ assemblies that exert different toxicity depending on their form. Thus, little is yet known about why antibodies that have been approved as drugs are effective.

What is important now is to understand the underlying cause and to develop treatments to eliminate it.

We have studied the various forms of Aβ assemblies and their roles for many years. As a result, we discovered that when about 30 molecules of Aβ aggregate together, they form an ordered sphere with spines like a sea urchin. These spheres have a strong toxicity and destroy neurons and neuronal networks. We named these sea urchin-like toxic spheres “amylospheroids” (ASPD). We further discovered that the spines on ASPD bind to the sodium pump, which is essential for the function and survival of neurons, leading to the death of the neurons. Thus, for the first time, one of the causes of Alzheimer's disease was identified. Once this was established, several treatment strategies could be considered, including blocking ASPD binding to the sodium pump or removing ASPD themselves. We are currently working along these lines, collaborating with researchers from other fields. Our ultimate aim is to prevent the disease so that people need not fear dementia and can live a good and healthy life as they age.

Our main current ongoing projects are:


March 18, 2022

The study protocol newly created by our research group was published in the American academic journal STAR Protocols. (Sasahara T., and Hoshi M., High-throughput screening for agonists of ROS production in live human vascular endothelial cells. Star Protoc., 3(1):101053. doi: 10.1016/j.xpro.2021.101053)

September 24, 2021

Our research group’s research results were published in iScience, the American academic journal. (Sasahara T., Satomura K., Tada M., Kakita A., and Hoshi M., Alzheimer’s Aβ assembly binds sodium pump and blocks endothelial NOS activity via ROS-PKC pathway in brain vascular endothelial cells. iScience, 24(9):102936. doi: 10.1016/j.isci.2021.102936)

February 3, 2021

A research review written by Prof. M. Hoshi was published in the American academic journal, British Journal of Pharmacology. This research review was highly evaluated and was featured on the cover page. (Hoshi M., Multi-angle development of therapeutic methods for Alzheimer’s disease. Br. J. Pharmacol., 178(4):770-783. doi: 10.1111/bph.15174)

November 1, 2020

The research results of our research group were published in the American academic journal, Journal of Comparative Neurology. (Murata K., Kinoshita T., Ishikawa T., Kuroda K., Hoshi M., and Fukazawa Y., Region- and neuronal-subtype-specific expression of Na,K-ATPase alpha and beta subunit isoforms in the mouse brain. J. Comp. Neurol., 528(16):2654-2678. doi: 10.1002/cne.24924)

January 10, 2020

The research results of our research group were published in the American academic journal, Journal of Biological Chemistry. (Xiao Y., Matsuda I., Inoue M., Sasahara T., Hoshi M., and Ishii Y., NMR-based site-resolved profiling of β-amyloid misfolding reveals structural transitions from pathologically relevant spherical oligomer to fibril. J. Biol. Chem., 295(2):458-467. doi: 10.1074/jbc.RA119.008522)