{"title":"[Development of drug discovery support system using chemoinformatics and generative AI technology].","authors":"Atsushi Yoshimori","doi":"10.1254/fpj.24094","DOIUrl":"10.1254/fpj.24094","url":null,"abstract":"<p><p>In recent years, the rapid development of generative AI has given rise to a variety of services such as machine translation, sentence summarization, and programming code generation. In drug discovery, generative AI and chemoinformatics have been used for seed/lead compound generation and optimization, and several successful cases were reported. The use of AI technology in drug discovery is expected to solve previously difficult problems and dramatically improve success rate in drug discovery. ITM, Inc. is a venture company established in 2004 to support drug discovery in silico using original chemoinformatics technology. Currently, ITM is developing a drug discovery support system that combines state-of-the-art AI technology and chemoinformatics technology. This paper introduces ITM's technology with a focus on the use of generative AI.</p>","PeriodicalId":12208,"journal":{"name":"Folia Pharmacologica Japonica","volume":"160 2","pages":"120-126"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143536989","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}
{"title":"[Therapeutic applications of engineered microglia for central nervous system disorders].","authors":"Yoki Nakamura","doi":"10.1254/fpj.25042","DOIUrl":"https://doi.org/10.1254/fpj.25042","url":null,"abstract":"","PeriodicalId":12208,"journal":{"name":"Folia Pharmacologica Japonica","volume":"160 5","pages":"374"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144948207","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}
{"title":"[Recent findings on the heterogeneity of astrocytes].","authors":"Yuta Kohro","doi":"10.1254/fpj.25024","DOIUrl":"https://doi.org/10.1254/fpj.25024","url":null,"abstract":"","PeriodicalId":12208,"journal":{"name":"Folia Pharmacologica Japonica","volume":"160 4","pages":"306"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144552782","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}
{"title":"[Clinical features of JAK1 gain-of-function variants and perspectives on monogenic disorders in allergic diseases].","authors":"Kenji Toyokuni, Satoshi Fujita, Hideaki Morita","doi":"10.1254/fpj.25011","DOIUrl":"10.1254/fpj.25011","url":null,"abstract":"<p><p>The prevalence of allergic diseases is increasing worldwide, with approximately one in two individuals in Japan affected by some form of allergic condition, making it a common disease. While most allergic diseases are multifactorial, involving a complex interplay between genetic predispositions and environmental factors, a subset of cases is attributed to monogenic disorders, which have been increasingly reported in recent years. This article focuses on JAK1 gain-of-function (GOF) variants, highlighting their clinical features, therapeutic potential, and the future prospects of research on monogenic disorders in allergic diseases. JAK1-GOF variants are characterized by early onset and severe atopic dermatitis that does not respond to conventional therapies. They are also frequently associated with other allergic diseases, such as food allergies and asthma, as well as autoimmune diseases and growth impairments. JAK inhibitors represent a promising therapeutic option for JAK1-GOF mutations, with previous reports suggesting their efficacy. Predicting drug efficacy through in vitro studies could enable the selection of tailored treatments for individual patients, potentially leading to significant clinical improvements. It is hypothesized that undiagnosed patients with such monogenic disorders may exist. Accurate diagnosis of these patients could facilitate effective treatments. Moreover, research on monogenic disorders has the potential to lead to the development of novel molecular-targeted therapies through the elucidation of disease pathophysiology, benefiting not only patients with rare genetic disorders but ultimately a broader population.</p>","PeriodicalId":12208,"journal":{"name":"Folia Pharmacologica Japonica","volume":"160 4","pages":"239-243"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144552752","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}
{"title":"[Glial dysfunction-mediated pathogenesis of glaucoma].","authors":"Youichi Shinozaki","doi":"10.1254/fpj.25030","DOIUrl":"10.1254/fpj.25030","url":null,"abstract":"<p><p>Glaucoma is the leading cause of blindness worldwide. Vision loss in glaucoma is caused by damage to retinal ganglion cells (RGCs), which are responsible for transmitting visual information from the retina to the brain. Glaucoma is a multifactorial disease with multiple risk factors, among which elevated intraocular pressure (IOP) is the most well-established. Currently, lowering IOP is the mainstay of glaucoma treatment. However, disease progression is frequently observed even in patients whose IOP is well controlled. Notably, the majority of Japanese glaucoma patients are diagnosed with normal-tension glaucoma (NTG). These observations highlight the urgent need to elucidate IOP-independent mechanisms contributing to glaucoma pathogenesis. In this context, increasing attention has been directed toward the potential role of glial cells in the development and progression of glaucoma. Glial cells are known to play critical roles in various neurodegenerative diseases. In glaucoma, glial activation and dysfunction have been documented in the ocular tissue of human patients, as well as in primate and rodent models. Importantly, glial activation is observed at early stages of glaucoma, even before detectable RGC loss occurs. This raises the possibility that glial dysfunction is not merely a secondary response to neuronal injury but may serve as a primary driver of disease onset. For example, deletion of glial cell-specific genes has been shown to induce NTG-like phenotypes. This article provides an overview of recent advances in our understanding of the role of glial cells in glaucoma pathogenesis, with a focus on insights gained from our own research.</p>","PeriodicalId":12208,"journal":{"name":"Folia Pharmacologica Japonica","volume":"160 5","pages":"342-346"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144948214","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}
{"title":"[Behavior analysis of adult zebrafish for the assessment of anxiety, aggression, and sociability].","authors":"Sakyo Yasojima, Hiroaki Ito, Junko Koiwa, Yuhei Nishimura","doi":"10.1254/fpj.25031","DOIUrl":"10.1254/fpj.25031","url":null,"abstract":"<p><p>Various behavior analysis methods have been developed using different animal species to elucidate the pathophysiology of behavioral abnormalities in humans and develop therapeutic agents. The development of behavior analysis methods using zebrafish has also been progressing, and a substantial body of knowledge has been accumulated. In this paper, we introduce the Novel tank test for assessing anxiety, the Mirror biting test for assessing aggression, and the Social interaction test for assessing sociality. These methods are relatively easy to implement in ordinary laboratories. We also discuss the problems associated with behavioral analyses using zebrafish. For example, zebrafish strains frequently used in behavioral analyses are not inbred, such as C57BL/6 in mice and F344 in rats. There are differences among the zebrafish strains in terms of cortisol levels, neural marker expression, and behavior characteristics. The housing and husbandry of zebrafish also vary among laboratories. Standardizing these factors is important to increase the reproducibility and replicability of zebrafish neurobehavioral research. Understanding the characteristics of each method and selecting the appropriate behavior analysis method according to the purpose will facilitate the understanding of the pathophysiology of human diseases and the development of new treatments.</p>","PeriodicalId":12208,"journal":{"name":"Folia Pharmacologica Japonica","volume":"160 5","pages":"347-351"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144948234","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}
{"title":"[Aβ Receptor PirB and its regulation by LOTUS].","authors":"Yuki Kawaguchi, Kohtaro Takei","doi":"10.1254/fpj.25018","DOIUrl":"10.1254/fpj.25018","url":null,"abstract":"<p><p>Over the years, research has accumulated a vast amount of knowledge about the pathogenesis of dementia, including Alzheimer's disease (AD). However, fundamental treatments for AD have not yet been established. In this article, we discuss an Aβ receptor, paired immunoglobulin like receptor B (PirB) and its endogenous regulator lateral olfactory tract usher substance (LOTUS), which are completely different novel drug target from existing drugs, and the possibility of endogenous inhibitors of PirB. PirB expressed in neurons is a negative regulator of neuronal plasticity, as loss or inhibition of PirB increases neuronal plasticity, leading to increased spine density and improved cognitive function. Furthermore, PirB is known to function as a receptor for Aβ, leading to reduced neuronal plasticity and cell death. These findingss suggest that PirB can be positioned as a novel drug target for the treatment of AD. The neuronal circuit-forming factor LOTUS, which binds to PirB and functions as an endogenous antagonist, has been shown to inhibit the neurotoxic effects of Aβ mediated by PirB. Namely, LOTUS is an endogenous molecule that inhibits Aβ receptor function of PirB and may have medicinal effects against Aβ pathology.</p>","PeriodicalId":12208,"journal":{"name":"Folia Pharmacologica Japonica","volume":"160 5","pages":"318-323"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144948258","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}