Folia Pharmacologica Japonica最新文献_第10页

[Targeting NAD metabolism in neuroendocrine carcinoma]. [针对神经内分泌癌的NAD代谢]。

Folia Pharmacologica Japonica Pub Date : 2025-01-01 DOI: 10.1254/fpj.24068

Nobuhiro Tanuma

{"title":"[Targeting NAD metabolism in neuroendocrine carcinoma].","authors":"Nobuhiro Tanuma","doi":"10.1254/fpj.24068","DOIUrl":"https://doi.org/10.1254/fpj.24068","url":null,"abstract":"NAD is an important metabolite that functions as a cofactor in various metabolic reactions, and its biosynthesis is known to be upregulated during malignant transformation. The NAD salvage, in which NAMPT is a rate-limiting enzyme, is a predominant pathway for NAD synthesis in most tissues including cancer. However, less is known about how cancer sensitivity against NAMPT inhibition (NAMPTi) is dictated. Here we report that lung and prostate neuroendocrine carcinomas (NECs) are extremely vulnerable to NAMPTi and that the therapeutic effect of NAMPTi is markedly enhanced by dietary restriction of the NAD precursor, niacin. We found that de novo NAD synthesis is inactivated during neuroendocrine differentiation of tumor cells, leading to a high dependence of NEC cells on NAD salvage. Further investigations in mouse transplantation models showed that lowering blood levels of nicotinic acid riboside (NAR), one of the non-classical niacin, dramatically increases the therapeutic effect of NAMPTi on NEC. Metabolic studies showed that dietary nicotinic acid is converted to NAR and then released into the circulation, and NAD synthesis using NAR substrates can compensate for the effects of NAMPTi in tumor cells. These findings reveal that niacin restriction with NAMPTi is synthetic lethal to NECs.","PeriodicalId":12208,"journal":{"name":"Folia Pharmacologica Japonica","volume":"160 4","pages":"261-267"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144552784","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 : 2025-01-01 DOI: 10.1254/fpj.25015

Masato Tsutsui, Tadashi Kaname

引用次数: 0

[Preface]. (前言)。

Folia Pharmacologica Japonica Pub Date : 2025-01-01 DOI: 10.1254/fpj.24116

Nariko Arimura, Tomoko Wakabayashi

引用次数: 0

[The involvement of gut microbiota on nociplastic pain]. [肠道菌群与致伤性疼痛的关系]。

Folia Pharmacologica Japonica Pub Date : 2025-01-01 DOI: 10.1254/fpj.25038

Yuta Kohro

引用次数: 0

[Microglia-mediated cognitive impairment induced by methamphetamine]. [甲基苯丙胺引起的小胶质细胞介导的认知障碍]。

Folia Pharmacologica Japonica Pub Date : 2025-01-01 DOI: 10.1254/fpj.25032

Naotaka Izuo, Yuka Kusui, Atsumi Nitta

{"title":"[Microglia-mediated cognitive impairment induced by methamphetamine].","authors":"Naotaka Izuo, Yuka Kusui, Atsumi Nitta","doi":"10.1254/fpj.25032","DOIUrl":"10.1254/fpj.25032","url":null,"abstract":"More than half of chronic methamphetamine (METH) users exhibit multi-domain cognitive deficits, including impaired attention, executive function, and memory. MRI studies consistently demonstrate hippocampal atrophy and frontotemporal cortical thinning; these structural changes spatially overlap with glial activation, indicating the coexistence of morphological damage and ongoing neuroinflammation. To clarify causality, we developed a mouse model in which low-dose METH is micro-infused into the nucleus accumbens. The mice displayed cognitive dysfunction and hippocampal long-term potentiation deficits together with microglial activation and mRNA up-regulation of IL-1β and the complement component C1q. Suppressing microglial activation with minocycline normalized these soluble factors and restored cognitive function. Complement proteins drive microglia-mediated synaptic pruning, and their over-activation has been implicated in Alzheimer's disease and schizophrenia. Taken together, our findings suggest that METH-induced cognitive impairment is mediated by abnormal microglial pruning via complement signaling. This review summarizes the clinical phenotype of METH-related cognitive dysfunction, integrates preclinical findings, and proposes novel therapeutic avenues that target microglial activation.","PeriodicalId":12208,"journal":{"name":"Folia Pharmacologica Japonica","volume":"160 5","pages":"330-333"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144948190","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

[Age-related brain functional changes and microglia]. [与年龄相关的脑功能变化和小胶质细胞]。

Folia Pharmacologica Japonica Pub Date : 2025-01-01 DOI: 10.1254/fpj.25033

Yoki Nakamura, Kazue Hisaoka-Nakashima, Norimitsu Morioka

{"title":"[Age-related brain functional changes and microglia].","authors":"Yoki Nakamura, Kazue Hisaoka-Nakashima, Norimitsu Morioka","doi":"10.1254/fpj.25033","DOIUrl":"10.1254/fpj.25033","url":null,"abstract":"Age-related alterations in brain function are considered a physiological phenomenon that everyone may experience as a decline in memory and cognitive abilities. However, the rate of progression varies among individuals, and the underlying mechanisms remain largely unclear. Microglia, the resident immune cells of the brain, play a crucial role in maintaining central nervous system homeostasis through diverse functions such as phagocytosis of cellular debris, synaptic pruning, and regulation of neuroinflammatory responses. Previous studies have demonstrated that the cellular morphology of microglia undergoes significant changes with age. Furthermore, recent advances in RNA sequencing analysis techniques have revealed that microglia are not a homogeneous cell population but rather consist of diverse subpopulations. Notably, white matter-associated microglia (WAM) and interferon-response microglia (IRM) are reported to increase in proportion with aging. Thus, aging induces complex changes in the morphology, function, and subpopulation composition of microglia, which may impair the homeostatic maintenance of brain and contribute to age-related alterations in brain function, such as cognitive decline. This review focuses on the impact of aging on microglia and their association with changes in brain function, presenting the latest findings in this field.","PeriodicalId":12208,"journal":{"name":"Folia Pharmacologica Japonica","volume":"160 5","pages":"338-341"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144948261","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

[Pharmacological characteristics and clinical effectiveness of Futibatinib (Lytgobi_® Tablets), a covalently-binding, irreversible FGFR1-4 inhibitor]. [共价结合的不可逆 FGFR1-4 抑制剂 Futibatinib（Lytgobi® 片）的药理特性和临床疗效】。］

Folia Pharmacologica Japonica Pub Date : 2024-11-01 Epub Date: 2024-10-10 DOI: 10.1254/fpj.24045

Katsuya Takagaki, Ryota Okude, Naoki Hirayama, Hiroshi Sootome, Hiroshi Hirai

{"title":"[Pharmacological characteristics and clinical effectiveness of Futibatinib (Lytgobi® Tablets), a covalently-binding, irreversible FGFR1-4 inhibitor].","authors":"Katsuya Takagaki, Ryota Okude, Naoki Hirayama, Hiroshi Sootome, Hiroshi Hirai","doi":"10.1254/fpj.24045","DOIUrl":"10.1254/fpj.24045","url":null,"abstract":"Futibatinib (Lytgobi® Tablets 4 ‍mg), a novel fibroblast growth factor receptor (FGFR) inhibitor developed by Taiho Pharmaceutical using the Cysteinomix Drug Discovery Platform, was approved in Japan in June 2023 for the treatment of patients with unresectable biliary tract cancer with FGFR2 fusion or rearrangement that had progressed after at least one prior chemotherapy. Futibatinib covalently binds to the cysteine residue in the FGFR kinase domain P-loop structure and is believed to exert antitumor activity by selectively and irreversibly inhibiting FGFR1-4. Many FGFR inhibitors under development are ATP-competitive; however, futibatinib is the first approved covalently-binding irreversible FGFR inhibitor. It inhibits cell proliferation by inhibiting FGFR phosphorylation and its downstream signaling pathways in cancer cell lines. Futibatinib showed inhibitory activity against a wider range of FGFR mutants than ATP-competitive, reversible FGFR inhibitors and inhibited cell proliferation without significantly deviating from the inhibitory effect on wild-type FGFR. Futibatinib showed antitumor efficacy in mice subcutaneously transplanted with human tumor cell lines driven by FGFR. The international phase 2 study (TAS-120-101) was conducted in patients with refractory intrahepatic cholangiocarcinoma with FGFR2 fusion or rearrangement. The overall response rate was 41.7%, showing consistent efficacy regardless of co-occurring genomic alterations. Although some typical FGFR inhibitor-related side effects were observed, they were manageable and futibatinib had a good safety profile. Futibatinib is an important drug for biliary tract cancer, which has limited treatment options; its development is underway for other types of cancer, and it is expected to benefit more patients.","PeriodicalId":12208,"journal":{"name":"Folia Pharmacologica Japonica","volume":" ","pages":"423-432"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142389220","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

医学　薬学　薬理学医学药学药理学

Folia Pharmacologica Japonica Pub Date : 2024-07-01 DOI: 10.1254/fpj.24028

Motokazu Koga

引用次数: 0

[Canine inherited retinal degeneration as model to study disease mechanisms and therapy for ciliopathies]. [以犬遗传性视网膜变性为模型，研究纤毛疾病的发病机制和治疗方法］

Folia Pharmacologica Japonica Pub Date : 2024-07-01 Epub Date: 2024-04-26 DOI: 10.1254/fpj.23071

Kei Takahashi, Keiko Miyadera

{"title":"[Canine inherited retinal degeneration as model to study disease mechanisms and therapy for ciliopathies].","authors":"Kei Takahashi, Keiko Miyadera","doi":"10.1254/fpj.23071","DOIUrl":"10.1254/fpj.23071","url":null,"abstract":"Humans have a highly developed retina and obtain approximately 80% of their external information from vision. Photoreceptor cells, which are located in the outermost layer of the neuroretina and recognize light signals, are highly specialized sensory cilia that share structural and functional features with primary cilia. Genetic disorders of the retina or photoreceptor cells are termed inherited retinal diseases (IRDs) and are caused by variants in one of more than 280 genes identified to date. Among the genes responsible for IRDs, many are shared with those responsible for ciliopathies. In studies of inherited diseases, mouse models are commonly used due to their advantages in breeding, handling, and relative feasibility in creating pathological models. On the other hand, structural, functional, and genetic differences in the retina between mice and humans can be a barrier in IRD research. To overcome the limitations of mouse models, larger vertebrate models of IRDs can be a useful research subject. In particular, canines have retinas that are structurally and functionally similar and eyes that are anatomically comparable to those of humans. In addition, due to their unique veterinary clinical surveillance and genetic background, naturally occurring canine IRDs are more likely to be identified than in other large animals. To date, pathogenic mutations related to canine IRDs have been identified in more than 30 genes, contributing to the understanding of pathogeneses and to the development of new therapies. This review provides an overview of the roles of the canine IRD models in ciliopathy research.","PeriodicalId":12208,"journal":{"name":"Folia Pharmacologica Japonica","volume":" ","pages":"192-197"},"PeriodicalIF":0.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140862622","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

[Role of endosomal pathway in the ciliary transport and the membrane organization of outer segment disc membrane in photoreceptors]. [内体途径在光感受器睫状体运输和外节盘膜组织中的作用]。

Folia Pharmacologica Japonica Pub Date : 2024-07-01 Epub Date: 2024-04-26 DOI: 10.1254/fpj.23077

Wataru Otsu

{"title":"[Role of endosomal pathway in the ciliary transport and the membrane organization of outer segment disc membrane in photoreceptors].","authors":"Wataru Otsu","doi":"10.1254/fpj.23077","DOIUrl":"10.1254/fpj.23077","url":null,"abstract":"A photoreceptor is a specialized neuron that is responsible for the conversion of light into an electrical signal. Photoreceptors are classified into rods and cones, and both photoreceptors possess light-sensing ciliary organelles called outer segments (OSs), anchored in the cells by a microtubule-based axoneme. The OS consists of a stack of disc membranes, which are abundant for the retinal phototransduction proteins such as rhodopsin. Recently, modern protein synchronization techniques using in vivo transfection in rodents revealed that rhodopsin transits through Rab11-positive recycling endosomes, preferentially entering the OS in the dark. Moreover, Peripherin-2 (PRPH2, also called retinal degeneration slow, RDS), a photoreceptor-specific tetraspanin protein essential for the morphogenesis of disc membranes, is delivered to the OS following complementary to that of rhodopsin. Various PRPH2 disease-causing mutations have been found in humans, and most of the mutations in the cytosolic C-terminus of PRPH2 are linked to cone-dominant macular dystrophies. It has been shown that the late endosome is the waystation that sorts newly synthesized PRPH2 into the cilium. The multiple C-terminal motifs of PRPH2 regulate its late endosome and ciliary targeting through ubiquitination and binding to an Endosomal Sorting Complexes Required for Transport (ESCRT) component, Hrs. These findings suggest that the late endosomes play an important role in the biosynthetic pathway of ciliary proteins and can be a new therapeutic target for the diseases caused by ciliary defects.","PeriodicalId":12208,"journal":{"name":"Folia Pharmacologica Japonica","volume":" ","pages":"203-208"},"PeriodicalIF":0.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140864378","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