Research News

Protein aggregation inhibitor shows lower levels of cell death and paralysis in mice with acute strokes

Beneficial effects of GAPDH-C152A expression and GAI-17 on acute ischemic stroke treatment in model mice

Ischemia-Reperfusion-induced GAPDH aggregates lead to cell death and paralysis, but both GAPDH-C152A expression and GAI-17 treatment can decrease the chances of post-stroke side effects.

Credit: Osaka Metropolitan University

Stroke is said to be the second leading cause of death worldwide after heart disease. To prevent the death of neurons in the brain, a research group led by Osaka Metropolitan University Associate Professor Hidemitsu Nakajima of the Graduate School of Veterinary Science has developed a drug that inhibits a protein involved in cell death.

The multifunctional protein GAPDH (glyceraldehyde-3-phosphate dehydrogenase) is linked to pathogenesis in many intractable brain and nervous system diseases. The team developed GAI-17, a GAPDH aggregation inhibitor. When this inhibitor was administered to model mice with acute strokes, there was a significantly lower level of brain cell death and paralysis compared to untreated mice.

GAI-17 also showed no side effects of concern, such as adverse effects on the heart or cerebrovascular system. Furthermore, experiments using GAI-17 showed improvement in the mice even when administered six hours after a stroke.

“The GAPDH aggregation inhibitor we have developed is expected to be a single drug that can treat many intractable neurological diseases, including Alzheimer’s disease,” stated Professor Nakajima. “Going forward, we will verify the effectiveness of this approach in disease models other than stroke and promote further practical research toward the realization of a healthy and long-lived society.”

The findings were published in iScience.

Funding

This work was supported by MEXT/JSPS KAKENHI in a Grant-in-Aid to H.N. (JP25450428, JP19580346, and JP16H05029) and T.H. (JP23K24205 and JP25K02547), a Grant-in-Aid for Challenging Research to H.N. (Exploratory; JP17K19330) and to H.T. (Exploratory; JP23K18163), and the Collaborative Research Program of Institute for Protein Research, the University of Osaka, to T.H. (ICR-24-03), and by AMED to H.N. (grant number JP23ym0126815) and T.H. (grant numbers JP21wm0425010 and JP21gm1510006).

Paper Information

Journal: iScience
Title: Inhibition of GAPDH aggregation as a potential treatment for acute ischemic stroke
DOI: 10.1016/j.isci.2025.112564
Author: Masanori Itakura, Takeya Kubo, Akihiro Kaneshige, Masatoshi Nakatsuji, Naoki Harada, Ryoichi Yamaji, Takatoshi Hikida, Takashi Inui, and Hidemitsu Nakajima
Published: 2 May2025
URL: https://doi.org/10.1016/j.isci.2025.112564

Contact

Hidemitsu Nakajima
Graduate School of Veterinary Science
Email: h_nakajima[at]omu.ac.jp

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