The novel mitochondria activator, 10-ethyl-3-methylpyrimido[4,5-b]quinoline-2,4(3H,10H)-dione (TND1128), promotes the development of hippocampal neuronal morphology

Shutaro Katsurabayashi; Kohei Oyabu; Kaori Kubota; Takuya Watanabe; Tomohisa Nagamatsu; Norio Akaike; Katsunori Iwasaki

doi:10.1016/j.bbrc.2021.04.132

The novel mitochondria activator, 10-ethyl-3-methylpyrimido[4,5-b]quinoline-2,4(3H,10H)-dione (TND1128), promotes the development of hippocampal neuronal morphology

Biochem Biophys Res Commun. 2021 Jun 30:560:146-151. doi: 10.1016/j.bbrc.2021.04.132. Epub 2021 May 12.

Authors

Shutaro Katsurabayashi¹, Kohei Oyabu², Kaori Kubota³, Takuya Watanabe³, Tomohisa Nagamatsu⁴, Norio Akaike⁵, Katsunori Iwasaki³

Affiliations

¹ Department of Neuropharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University, 8-19-1 Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan. Electronic address: shutarok@fukuoka-u.ac.jp.
² Department of Neuropharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University, 8-19-1 Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan.
³ Department of Neuropharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University, 8-19-1 Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan; A.I.G. Collaborative Research Institute for Aging and Brain Sciences, Fukuoka University, 8-19-1 Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan.
⁴ Laboratory of Curative Medicine Creation Study for Geriatric-diseases Prevention, Faculty of Pharmaceutical Sciences, Sojo University, 4-22-1 Ikeda, Nishi-ku, Kumamoto, 860-0082, Japan; Chemiteras, Inc., 3-24-5 Shin-yokohama, Kohoku-ku, Yokohama, Kanagawa, 222-0033, Japan.
⁵ Chemiteras, Inc., 3-24-5 Shin-yokohama, Kohoku-ku, Yokohama, Kanagawa, 222-0033, Japan; Research Division for Clinical Pharmacology, Medical Corporation, Juryo Group, Kumamoto Kinoh Hospital, 6-8-1 Yamamuro, Kita-ku, Kumamoto, 860-8518, Japan; Research Division of Neurophysiology, Kitamoto Hospital, 3-7-6, Kawarasone, Koshigaya, Saitama, 343-0821, Japan.

PMID: 33989906
DOI: 10.1016/j.bbrc.2021.04.132

Abstract

Adenosine triphosphate (ATP) is the most vital energy source produced mainly in the mitochondria. Age-related mitochondrial dysfunction is associated with brain diseases. Nicotinamide adenine dinucleotide (NAD⁺) is an essential cofactor for energy production in mitochondria. Here, we examined how the novel NAD⁺-assisting substance, 10-ethyl-3-methylpyrimido[4,5-b]quinoline-2,4(3H,10H)-dione (TND1128), modulates the morphological growth of cultured mouse hippocampal neurons. The morphological growth effect of TND1128 was also compared with that of β-nicotinamide mononucleotide (β-NMN). TND1128 induced the branching of axons and dendrites, and increased the number of excitatory synapses. This study provides new insight into TND1128 as a mitochondria-stimulating drug for improving brain function.

Keywords: Axon; Dendrite; Development; Mitochondria; Synapse.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Axons / drug effects
Axons / ultrastructure
Cells, Cultured
Dendrites / drug effects
Dendrites / ultrastructure
Hippocampus / cytology*
Mice
Mice, Inbred ICR
Neurons / cytology
Neurons / drug effects*
Synapses / drug effects