1: CRMP2-binding compound, edonerpic maleate, accelerates motor function recovery from brain damage.

Science.

2018 Apr 6;360(6384):50-57. doi: 10.1126/science.aao2300.

Abe H, Jitsuki S, Nakajima W, Murata Y, Jitsuki-Takahashi A, Katsuno Y, Tada H, Sano A, Suyama K, Mochizuki N, Komori T, Masuyama H, Okuda T, Goshima Y, Higo N, Takahashi T.

Stroke often causes severe paralysis, greatly reducing patients' quality of life. Treatment aimed at restoring motor function during the recovery period after a stroke mainly consists of rehabilitation through steady training, but its effects are limited, and more effective treatments are desired. It is known that the mechanism of this motor function recovery involves changes in the brain (brain plasticity) in response to external stimuli such as rehabilitation. It has been shown that when synaptic responses are enhanced along with plastic changes such as memory and learning in the body, AMPA receptors, one of the receptors for the neurotransmitter glutamate, increase on the synaptic membrane. In this study, through joint research with Toyama Chemical Co., Ltd. of the Fujifilm Group, the National Institute of Advanced Industrial Science and Technology (AIST), and the National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), we identified a candidate compound for a new drug (edonerpic maleate) that significantly promotes the effects of rehabilitation after a stroke. Using rodents and cynomolgus monkeys, we demonstrated that this compound promotes the synaptic translocation of AMPA receptors and dramatically enhances training-dependent motor function recovery after brain injury (Figure). Preparations for clinical trials are currently underway, and it is expected to lead to innovations in stroke medical care.

(Takuya Takahashi, Professor of Physiology, Yokohama City University, 74th graduating class)

CELL METABOLISM,

27 (3):513-528; 10.1016/j.cmet.2017.11.002 MAR 6 2018

Yoshino Jun, Baur Joseph A., Imai Shin-ichiro

It is no exaggeration to say that research in NAD+ biology, which has a history of over 110 years, is currently centered on the effects of two NAD+ intermediates: nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN). Recent research findings have led to a consensus that in a wide range of species, including humans, systemic NAD+ levels decline with age, and this is deeply involved in the pathophysiology of aging and age-related diseases. And surprisingly, it has been successively reported that in experimental animal models, NR and NMN exert remarkable therapeutic effects on various age-related diseases such as diabetes and Alzheimer's disease (Figure 1). This review summarizes the diverse benefits of NR and NMN, and also discusses the differences in their pharmacokinetics in vivo, as well as the physiological significance of the systemic NAD+ synthesis control mechanism. Currently, the move toward clinical application of these NAD+ intermediates is accelerating on a global scale, and in Japan as well, the safety and efficacy of NMN in humans are being investigated, led by Professor Hiroshi Ito of the Department of Internal Medicine, School of Medicine. We sincerely hope that this review will be of assistance in planning and conducting these clinical studies, and at the same time, will lead to the next breakthrough in NAD+ biology research.

(Jun Yoshino, Washington University, 79th graduating class; Shin-ichiro Imai, 68th graduating class)