Folia Pharmacologica Japonica最新文献_第5页

[Active control of neural circuit synchrony via oligodendroglial lipid synthesis]. [通过少突胶质脂质合成主动控制神经回路同步性]。

Folia Pharmacologica Japonica Pub Date : 2026-01-01 DOI: 10.1254/fpj.26039

Daisuke Kato

{"title":"[Active control of neural circuit synchrony via oligodendroglial lipid synthesis].","authors":"Daisuke Kato","doi":"10.1254/fpj.26039","DOIUrl":"10.1254/fpj.26039","url":null,"abstract":"Myelin is increasingly recognized as a dynamic regulator of neural circuits, shifting the paradigm from a purely synaptic-centric view of brain plasticity. This report details how activity-dependent changes in myelin lipid composition optimize neural circuit synchrony during motor learning. Using a mouse model with subtle myelin structural deficits, we demonstrate that impaired myelin regulation leads to increased temporal dispersion of axonal conduction. This asynchrony reduces the signal-to-noise ratio of neural activity in the primary motor cortex, thereby hindering motor skill acquisition. Crucially, optogenetic synchronization of thalamocortical inputs rescues these learning deficits, confirming that temporal precision is vital for plasticity. Furthermore, imaging mass spectrometry revealed stage-specific shifts in myelin lipid composition during motor learning. Sphingomyelin levels rise during the early phase, while galactosylceramide levels increase during the middle-to-late stages. Targeted suppression of the galactosylceramide-synthesizing enzyme in oligodendrocytes specifically impairs late-stage learning and increases conduction asynchrony without affecting gross myelin morphology. These findings suggest that oligodendrocytes actively fine-tune the timing of information arrival by modulating the lipid composition of myelin. These dynamic changes in myelin lipid composition represent a novel perspective on white matter plasticity essential for optimizing neural circuit outputs and behavior, offering new insights into neuropsychiatric disorders characterized by impaired neural synchrony.","PeriodicalId":12208,"journal":{"name":"Folia Pharmacologica Japonica","volume":"161 5","pages":"303-307"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148879588","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

[Is it possible to generate artificial mitochondrial genome?] 人造线粒体基因组有可能产生吗？］

Folia Pharmacologica Japonica Pub Date : 2026-01-01 DOI: 10.1254/fpj.25090

Ken-Ichi Wada

{"title":"[Is it possible to generate artificial mitochondrial genome?]","authors":"Ken-Ichi Wada","doi":"10.1254/fpj.25090","DOIUrl":"10.1254/fpj.25090","url":null,"abstract":"The mitochondrial genome (mtDNA) is a circular DNA of approximately 16.5 kbp, present at several thousand copies per cell. Although mtDNA is extremely small compared with the nuclear genome, it is quite important for life system because it encodes components essential for ATP production through oxidative phosphorylation. Since mtDNA mutations are thought to be implicated in a wide range of diseases, gene therapies targeting mtDNA are expected to provide promising treatment options for such disorders; however, current methods allow only limited manipulation of mtDNA. In this article, our recent efforts toward establishing mtDNA writing, a technology that would enable unrestricted and precise manipulation of mtDNA, are introduced. We hypothesized that creation of specialized host cells that preferentially accept exogenous mtDNA would be the key to achieving mtDNA writing. We named such host cells \"e-mt cells\" and assumed that cells maintaining a deviated type of mtDNA in a homoplasmic state could function as e-mt cells. To create e-mt cells, we developed a novel mitochondrial transfer method using a microfluidic device. This microfluidic device allowed direct and non-invasive mitochondrial transfer between live single cells by fusing them through a micro aperture (microslit/microtunnel). Furthermore, we successfully demonstrated single-mitochondrion transfer as well as cybrid generation via mitochondrial transfer into ρ0 cells. These findings suggest that the microfluidic device has the potential to achieve homoplasmic mtDNA modification through mtDNA cloning and is therefore expected to contribute to the creation of e-mt cells.","PeriodicalId":12208,"journal":{"name":"Folia Pharmacologica Japonica","volume":"161 4","pages":"216-221"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148367663","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Folia Pharmacologica Japonica Pub Date : 2026-01-01 DOI: 10.1254/fpj.26069

Kenji Sakamoto

引用次数: 0

[What astrocytic microstructure tells us about its physiology]. [星形细胞的微观结构告诉我们它的生理学]。

Folia Pharmacologica Japonica Pub Date : 2026-01-01 DOI: 10.1254/fpj.26040

Misa Arizono

{"title":"[What astrocytic microstructure tells us about its physiology].","authors":"Misa Arizono","doi":"10.1254/fpj.26040","DOIUrl":"https://doi.org/10.1254/fpj.26040","url":null,"abstract":"In neurons, fine morphological structures such as dendritic spines play a key role in maintaining synaptic input independence and enabling local, parallel signal processing, forming a fundamental basis of neuronal computation. In this context, it is well established that neuronal microstructure shapes the spatiotemporal properties of signaling. In contrast, although astrocytes, a type of glial cells, possess highly elaborate, densely ramified processes, the functional significance of their morphology has remained less clear. Astrocytic Ca2+ signals have long been described as slow and spatially diffuse, seemingly at odds with their fine structures. Recent advances in live super-resolution imaging have begun to bridge this gap by allowing direct visualization of perisynaptic astrocytic processes. Our studies suggest that astrocytic processes are not merely passive structural elements, but actively localize Ca2+ signals at individual synapses by regulating the diffusion of signaling molecules. Thus, astrocytes may, like neurons, exploit their morphology to control spatiotemporal signaling. Furthermore, such compartmentalization strategies may extend beyond the intracellular structure to the extracellular space surrounding neurons and astrocytes. The extracellular space has traditionally been examined only at a coarse, tissue-level resolution; however, advances in live super-resolution imaging have revealed a highly complex, heterogeneous geometry. This architecture is closely coupled to astrocytic microstructure and may influence local dynamics of transmitters and ions. In this review, we propose that microstructures outside neurons also contribute to shaping spatiotemporal signaling patterns through the regulation of molecular diffusion, and may even constitute the structural basis of brain information processing.","PeriodicalId":12208,"journal":{"name":"Folia Pharmacologica Japonica","volume":"161 5","pages":"308-312"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148879689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Folia Pharmacologica Japonica Pub Date : 2026-01-01 DOI: 10.1254/fpj.25089

Schuichi Koizumi

引用次数: 0

[Epigenetic remodeling mechanisms in heart failure and their pathological significance]. 心力衰竭的表观遗传重塑机制及其病理意义。

Folia Pharmacologica Japonica Pub Date : 2026-01-01 DOI: 10.1254/fpj.26032

Masafumi Funamoto

引用次数: 0

[Preface]. (前言)。

Folia Pharmacologica Japonica Pub Date : 2026-01-01 DOI: 10.1254/fpj.26058

Masaaki Ikeda

引用次数: 0

[Strategic evolution of drug discovery modalities: Tanabe Pharma's approach to immunology and oncology]. [药物发现模式的战略演变：Tanabe制药的免疫学和肿瘤学方法]。

Folia Pharmacologica Japonica Pub Date : 2026-01-01 DOI: 10.1254/fpj.25100

Ryuichi Totsuka

{"title":"[Strategic evolution of drug discovery modalities: Tanabe Pharma's approach to immunology and oncology].","authors":"Ryuichi Totsuka","doi":"10.1254/fpj.25100","DOIUrl":"10.1254/fpj.25100","url":null,"abstract":"Tanabe Pharma is advancing innovative drug discovery by selecting and designing optimal modalities based on disease characteristics, with a focus on neurological, immunological, and oncological disorders. This review outlines key initiatives in the immunology and oncology areas. In immunology, we promote \"Immunophenotype Drug Discovery\", which targets patients' immunological phenotypes. Based on a cross-disease understanding of pathophysiology, various modalities such as small molecules, antibodies, and functional proteins are selected. For the plasma cell-like phenotype, selective inhibitors of immunoproteasome components LMP7/LMP2 are being pursued. For the activated T cell-like phenotype, a fusion protein combining an IL-2 variant and an agonistic anti-TNFR2 antibody is under construction. In oncology, a novel modality, Targeted Protein Degradation (TPD), has been introduced to address \"undruggable\" targets that are difficult to control with conventional inhibitors. TPD induces degradation of target proteins via the ubiquitin-proteasome system by bringing them into proximity with E3 ubiquitin ligases using small molecules. Leveraging insights from the BRD4 inhibitor Y-803, we has developed MT-4561, which demonstrates high degradation activity and antitumor efficacy and is currently in Phase I clinical trials. These efforts exemplify a modality-driven drug discovery approach tailored to disease-specific pathologies, aiming to provide new therapeutic options for intractable diseases through the integration of scientific knowledge and technological innovation.","PeriodicalId":12208,"journal":{"name":"Folia Pharmacologica Japonica","volume":"161 3","pages":"150-157"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147835817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

[Therapeutic potential of histamine N-methyltransferase inhibition for the treatment of hypersomnia]. [抑制组胺n -甲基转移酶治疗嗜睡症的潜力]。

Folia Pharmacologica Japonica Pub Date : 2026-01-01 DOI: 10.1254/fpj.25070

Fumito Naganuma, Takeo Yoshikawa

{"title":"[Therapeutic potential of histamine N-methyltransferase inhibition for the treatment of hypersomnia].","authors":"Fumito Naganuma, Takeo Yoshikawa","doi":"10.1254/fpj.25070","DOIUrl":"10.1254/fpj.25070","url":null,"abstract":"Histamine plays a crucial role in maintaining wakefulness. Decreased histamine levels in the cerebrospinal fluid have been reported in patients with hypersomnia, including narcolepsy and idiopathic hypersomnia. Histamine N-methyltransferase (HNMT) is a key enzyme responsible for histamine degradation in the brain. In this study, we examined the effects of pharmacological HNMT inhibition on animal models of hypersomnia disorders. Metoprine, an HNMT inhibitor, significantly increased brain histamine levels and produced robust wake-promoting effects and suppressed cataplexy in narcolepsy model mice. The arousal effects of metoprine were mainly mediated through activation of histamine H1 receptors. Metoprine also promoted wakefulness in Sleepy mice, a model of idiopathic hypersomnia, and in drug-induced Parkinson's disease model mice. Compared with pitolisant, an H3 receptor inverse agonist that has been approved in EU and US for treatment of narcolepsy, metoprine exhibited stronger and more sustained wake-promoting effects. Our findings indicate that HNMT inhibitors increase brain histamine levels and promote wakefulness in various types of hypersomnia. Therefore, HNMT inhibitors may represent a novel and effective therapeutic approach for hypersomnia. To further advance drug development, we have performed high-throughput screening based on mass spectrometry, through which approximately 1,000 hit compounds have been identified.","PeriodicalId":12208,"journal":{"name":"Folia Pharmacologica Japonica","volume":"161 2","pages":"75-78"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147325214","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

[Mechanistic insights into maintenance and disruption of membrane phosphatidylserine asymmetry in human erythrocytes: a survival strategy during their lifespan]. [对人红细胞膜磷脂酰丝氨酸不对称的维持和破坏的机制见解：它们生命周期中的生存策略]。

Folia Pharmacologica Japonica Pub Date : 2026-01-01 DOI: 10.1254/fpj.26025

Momoko Seki, Nobuto Arashiki, Junichi Hoshino, Fumio Nakamura

{"title":"[Mechanistic insights into maintenance and disruption of membrane phosphatidylserine asymmetry in human erythrocytes: a survival strategy during their lifespan].","authors":"Momoko Seki, Nobuto Arashiki, Junichi Hoshino, Fumio Nakamura","doi":"10.1254/fpj.26025","DOIUrl":"10.1254/fpj.26025","url":null,"abstract":"Human erythrocytes retain phosphatidylserine (PS) only in the inner leaflet of plasma membranes during their 120-day lifespan to enforce membrane strengthen through associations with cytoskeletal proteins. Meanwhile, PS is exposed to the outer leaflet at the end of the lifespan for removal by phagocytosis of splenic macrophages. Consequently, their lifespan is determined by the localization of PS. PS-flippase activity of erythrocytes from an ATP11C-deficient patient was reduced by 90%, however, PS was unexposed in almost all erythrocytes from the patient. This suggests that flippase-independent mechanisms may retain PS in the inner leaflet. Depletion of cholesterol from erythrocyte membranes significantly facilitated PS exposure under low intracellular Ca2+ condition, indicating that cholesterol may block the lipid scrambling. In senescent erythrocytes, ATP11C level and the intracellular ATP and K+ concentrations were decreased in turn to reduce the flippase activity. The senescent erythrocytes easily exposed PS by raising a subtle amount of intracellular Ca2+ compared to young erythrocytes, indicating that the elevated intracellular Ca2+ concentration is a critical determinant of erythrocyte lifespan. We also assessed the erythrocytes from patients with renal anemia: the shortened lifespan of erythrocytes. We found that ATP11C expression level and the intracellular K+ concentration were decreased in the anemic erythrocytes, indicating that the early onset of aging is triggered by the PS exposure. Elucidating this mechanism would propose a novel treatment focused on extending erythrocyte's lifespan for renal anemia.","PeriodicalId":12208,"journal":{"name":"Folia Pharmacologica Japonica","volume":"161 4","pages":"249-252"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148367674","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0