論文

• Different Effects of Berberine Delivery to Mitochondria on Cells Derived from the Neural Crest
  Ikuma Hori, Hideyoshi Harashima, Yuma Yamada
  Biological and Pharmaceutical Bulletin, 47, 10, 1726, 1733, Pharmaceutical Society of Japan, 2024年10月26日, ［査読有り］, ［筆頭著者］
  研究論文（学術雑誌）
• Development of Liposomes That Target Axon Terminals Encapsulating Berberine in Cultured Primary Neurons
  Ikuma Hori, Hideyoshi Harashima, Yuma Yamada
  Pharmaceutics, 16, 1, 49, 49, MDPI AG, 2023年12月28日, ［査読有り］, ［筆頭著者］
  研究論文（学術雑誌）, Most of the energy in neurons is produced in mitochondria. Mitochondria generate the ATP that is essential for neuronal growth, function, and regeneration. Mitochondrial axonal transport plays a crucial role in maintaining neuronal homeostasis and biological activity. Decreased mitochondrial axonal transport at axon terminals, where the metabolism of substances is likely to be delayed, may contribute to neurological dysfunction. Therefore, regulation of mitochondrial dynamics at axon terminals has attracted considerable interest as a strategy to modulate neuronal function. Nanoparticles may be useful in controlling local mitochondrial dynamics. Nevertheless, there are few reports on the influence of drug delivery that nanoparticles impart on the mitochondrial dynamics in neurons. This paper reports the results of a study using liposomes (LPs) to examine local drug delivery and pharmacological actions on neurons. We tested berberine (BBR), which is an activator of AMP-activated protein kinase (AMPK), to examine the utility of this drug as a cellular energy sensor. Axon terminals targeting LPs were prepared. The amount of axon terminals targeting LPs was increased compared with treatment using cationic LPs. Moreover, axon terminal-targeting LPs increased anterograde transport by about 40% compared with that of either naked BBR or cationic LPs and suppressed axonal retraction. Our findings suggest that local drug delivery to neurons is important for enhancing pharmacological activity in axon terminals.
• Development of a Mitochondrial Targeting Lipid Nanoparticle Encapsulating Berberine
  Ikuma Hori, Hideyoshi Harashima, Yuma Yamada
  International Journal of Molecular Sciences, 24, 2, 903, 903, MDPI AG, 2023年01月04日, ［査読有り］, ［筆頭著者］
  研究論文（学術雑誌）, Delivering drugs to mitochondria, the main source of energy in neurons, can be a useful therapeutic strategy for the treatment of neurodegenerative diseases. Berberine (BBR), an isoquinoline alkaloid, acts on mitochondria and is involved in mechanisms associated with the normalization and regulation of intracellular metabolism. Therefore, BBR has attracted considerable interest as a possible therapeutic drug for neurodegenerative diseases. While BBR has been reported to act on mitochondria, there are few reports on the efficient delivery of BBR into mitochondria. This paper reports on the mitochondrial delivery of BBR using a lipid nanoparticle (LNP), a “MITO-Porter” that targets mitochondria, and its pharmacological action in Neuro2a cells, a model neuroblastoma. A MITO-Porter containing encapsulated BBR (MITO-Porter (BBR)) was prepared. Treatment with MITO-Porter (BBR) increased the amount of BBR that accumulated in mitochondria compared with a treatment with naked BBR. Treatment with MITO-Porter (BBR) resulted in increased ATP production in Neuro2a cells, which are important for maintaining life phenomena, compared with treatment with naked BBR. Treatment with MITO-Porter (BBR) also increased the level of expression of mitochondrial ubiquitin ligase (MITOL), which is involved in mitochondrial quality control. Our findings indicate that increasing the accumulation of BBR into mitochondria is important for inducing enhanced pharmacological actions. The use of this system has the potential for being important in terms of the regulation of the metabolic mechanism of mitochondria in nerve cells.
• Intermitochondrial signaling regulates the uniform distribution of stationary mitochondria in axons
  Nozomu Matsumoto, Ikuma Hori, Masashi K. Kajita, Tomoya Murase, Wataru Nakamura, Takahiro Tsuji, Seiji Miyake, Masaru Inatani, Yoshiyuki Konishi
  Molecular and Cellular Neuroscience, 119, 103704, 103704, Elsevier BV, 2022年03月, ［査読有り］, ［最終著者］
  研究論文（学術雑誌）