Journal of pharmacological sciences最新文献

Tacrolimus attenuates Th17 cell-mediated allergic skin inflammation in mice 他克莫司减轻小鼠Th17细胞介导的过敏性皮肤炎症

IF 2.9 3区医学 Q2 PHARMACOLOGY & PHARMACY

Journal of pharmacological sciences

Pub Date : 2026-01-12 DOI: 10.1016/j.jphs.2026.01.003

Fatemeh Beygom Mirkatouli , Yukiko Tao , Uyanga Enkhbaatar , Ryoken Yamanaka , Kento Miura , Norimasa Yamasaki , Sawako Ogata , Naohisa Hosomi , Akio Mori , Tomoharu Yasuda , Masaya Matsuda , Yuya Sannomiya , Takeshi Nabe , Tomofumi Numata , Kazumitsu Sugiura , Noriko Kitamura , Minoru Gotoh , Osamu Kaminuma

Tacrolimus, a topical calcineurin inhibitor, is used to treat atopic dermatitis (AD). AD is classically T helper type (Th) 2-driven, but Th17 cells are implicated in chronic AD, yet its efficacy against Th17-dependent pathology remains unclear. We investigated the effects of tacrolimus using a murine model of Th17-mediated allergic skin inflammation. In CD4⁺ T cells from DO11.10/Rag2^−/− mice, which express ovalbumin (OVA)-specific T cell receptor, tacrolimus differentially suppressed stimulation-induced cytokine expression by Th2 cells. At similar concentrations, tacrolimus suppressed Il21, but not Il17a or Il22, expression in Th17 cells. Subcutaneous OVA challenge elicited ear thickening in BALB/c mice after adoptive transfer of Th2 or Th17 cells, with a stronger response in Th17-transferred mice, but less than OVA-immunized controls. Topical tacrolimus reduced Th17-mediated ear swelling, corroborated by histopathology. In Th2-transferred mice, tacrolimus tended to reduce early skin thickening (day 3) but did not affect late responses (day 7). In Th17-transferred mice, tacrolimus significantly reduced allergen-specific T-cell accumulation in OVA-injected skin and tended to reduce Il21 expression, whereas Th2-cell accumulation and cytokine expression were unaffected. Tacrolimus exerts stronger inhibitory effects on Th17- than Th2-driven responses in this model, suggesting that suppression of Th17 pathways may contribute to its therapeutic benefit in AD.

他克莫司，局部钙调磷酸酶抑制剂，用于治疗特应性皮炎（AD）。AD是典型的T辅助型（Th） 2驱动的，但Th17细胞与慢性AD有关，但其对Th17依赖性病理的疗效尚不清楚。我们使用th17介导的过敏性皮肤炎症小鼠模型研究了他克莫司的作用。在表达卵清蛋白（OVA）特异性T细胞受体的DO11.10/Rag2−/−小鼠的CD4+ T细胞中，他克莫司差异抑制Th2细胞刺激诱导的细胞因子表达。在相同浓度下，他克莫司抑制Th17细胞中Il21的表达，但不抑制Il17a或Il22的表达。在过继性转移Th2或Th17细胞后，皮下OVA激发BALB/c小鼠的耳部增厚，Th17细胞转移小鼠的反应更强，但低于OVA免疫对照组。局部他克莫司减少th17介导的耳部肿胀，经组织病理学证实。在th2转移小鼠中，他克莫司倾向于减少早期皮肤增厚（第3天），但不影响晚期反应（第7天）。在th17转移小鼠中，他克莫司显著降低ova注射皮肤中过敏原特异性t细胞的积累，并倾向于降低il - 21的表达，而th2细胞的积累和细胞因子的表达不受影响。在该模型中，他克莫司对Th17-的抑制作用强于th2驱动的反应，表明抑制Th17通路可能有助于其治疗AD。

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引用次数: 0

DHODH inhibition impairs mitochondrial function and extravillous trophoblast invasion: Protective roles of quercetin and riboflavin DHODH抑制损害线粒体功能和外滋养细胞侵袭：槲皮素和核黄素的保护作用

IF 2.9 3区医学 Q2 PHARMACOLOGY & PHARMACY

Journal of pharmacological sciences

Pub Date : 2026-01-09 DOI: 10.1016/j.jphs.2026.01.001

Kanoko Yoshida, Kazuya Kusama, Kana Kanazawa, Yu Kawaguchi, Atsuya Tsuru, Mikihiro Yoshie, Kazuhiro Tamura

Hypertensive disorders of pregnancy (HDPs) are serious complications that pose significant risks to both maternal and fetal health. In HDP, placental circulatory impairment is generally attributed to defective differentiation and invasion of the human extravillous trophoblasts (EVTs). Our previous RNA-seq analysis of placentas from early-onset HDP patients revealed decreased expression of dihydroorotate dehydrogenase (DHODH), a mitochondrial enzyme involved in pyrimidine biosynthesis. DHODH inhibition is hypothesized to induce mitochondrial dysfunction. In this study, we investigated whether DHODH inhibition affects mitochondrial homeostasis and invasive capacity in EVT cell line. Selective DHODH inhibitors resulted in decreased mitochondrial membrane potential, upregulation of mitochondrial degradation factors, and mitochondrial fragmentation. Inhibition of DHODH or mitochondrial complexes I, II, and IV led to impaired cell invasion, accompanied by an increase in SA-β-gal-positive senescent cells. Treatment with quercetin or riboflavin, enhancers of mitochondrial ATP functions, partially restored invasive capacity and reduced senescent cell accumulation under mitochondrial stress conditions. Thus, DHODH inhibition in EVTs induces cellular senescence and diminished capacity for invasion. Mitochondrial activators such as quercetin and riboflavin may hold therapeutic promise for ameliorating the pathology of HDPs.

妊娠期高血压疾病（HDPs）是严重的并发症，对孕产妇和胎儿健康构成重大风险。在HDP中，胎盘循环障碍通常归因于人上皮外滋养细胞（EVTs）分化缺陷和侵袭。我们之前对早发HDP患者胎盘的RNA-seq分析显示，参与嘧啶生物合成的线粒体酶二氢羟酸脱氢酶（DHODH）表达降低。DHODH抑制被推测可诱导线粒体功能障碍。在这项研究中，我们研究了DHODH抑制是否影响EVT细胞系线粒体稳态和侵袭能力。选择性DHODH抑制剂导致线粒体膜电位降低，线粒体降解因子上调，线粒体断裂。抑制DHODH或线粒体复合物I、II和IV导致细胞侵袭受损，并伴有SA-β-gal阳性衰老细胞的增加。槲皮素或核黄素可增强线粒体ATP功能，可部分恢复线粒体应激条件下的侵袭能力，减少衰老细胞的积累。因此，在EVTs中抑制DHODH会导致细胞衰老和侵袭能力下降。线粒体激活剂如槲皮素和核黄素可能具有改善HDPs病理的治疗前景。

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引用次数: 0

SGLT2 inhibitor-induced glycosuria improves steatotic liver disease in parallel with enhanced ureagenesis in ob/ob mice 在ob/ob小鼠中，SGLT2抑制剂诱导的糖尿可改善脂肪变性肝病，同时增强尿原性

IF 2.9 3区医学 Q2 PHARMACOLOGY & PHARMACY

Journal of pharmacological sciences

Pub Date : 2025-12-24 DOI: 10.1016/j.jphs.2025.12.006

Satoshi Kidoguchi , Kento Kitada , Asahiro Morishita , Yudai Tsuji , Hiroyuki Ohsaki , Daisuke Yamazaki , Takashi Morikawa , Yoshio Konishi , Hideki Kobara , Takashi Yokoo , Jens Titze , Kazuo Takahashi , Akira Nishiyama

Purpose

Recent studies have reported that sodium-glucose cotransporter (SGLT) 2 inhibitors ameliorate steatotic liver disease. We investigated the contribution of SGLT2 inhibitor-induced fluid loss due to glycosuria in hepatic ureagenesis for water conservation to the association between improvement of steatotic liver disease and the energy-consuming nature of hepatic ureagenesis.

General methods

ob/ob mice fed a high-fat diet without carbohydrate restriction were administered luseogliflozin, an SGLT2 inhibitor, for eight weeks.

Findings

Luseogliflozin significantly decreased the liver weight, plasma aspartate aminotransferase and alanine aminotransferase levels, and fat content in mice with enhanced glycosuria (H-GlcV group). The ratio of urinary urea excretion decreased as a substitute for increased glucose excretion in the H-GlcV group. Luseogliflozin significantly increased liver urea content and tended to increase malate dehydrogenase (MDH)-1 activity. Liver MDH-1 activity was significantly positively correlated with liver urea content, suggesting that MDH-1-induced amino acid recruitment from the tricarboxylic acid cycle to the urea cycle may contribute to enhanced ureagenesis. In addition, liver weight was significantly negatively correlated with the liver urea content.

Conclusions

Our data suggest that enhanced hepatic ureagenesis as a compensatory water conservation mechanism for glycosuria-induced fluid loss may be associated with amelioration of steatotic liver disease in SGLT2 inhibitor-treated ob/ob mice.

最近的研究报道了钠-葡萄糖共转运蛋白（SGLT） 2抑制剂可改善脂肪变性肝病。我们研究了SGLT2抑制剂诱导的肝糖尿丢失在肝糖尿潴留过程中与脂肪肝疾病的改善和肝糖尿潴留的能量消耗之间的关系。一般方法：在不限制碳水化合物的情况下饲喂高脂肪饮食的小鼠，给予糖格列净（一种SGLT2抑制剂）8周。结果：糖尿增高组（H-GlcV组）小鼠肝脏重量、血浆天冬氨酸转氨酶和丙氨酸转氨酶水平及脂肪含量显著降低。在H-GlcV组中，尿尿素排泄比例降低，替代了葡萄糖排泄的增加。糖格列净显著提高肝脏尿素含量，并有增加苹果酸脱氢酶(MDH)-1活性的趋势。肝脏MDH-1活性与肝脏尿素含量显著正相关，表明MDH-1诱导氨基酸从三羧酸循环向尿素循环募集可能有助于增强尿素生成。肝脏重量与肝脏尿素含量呈极显著负相关。结论sour数据提示，SGLT2抑制剂治疗的ob/ob小鼠脂肪肝疾病的改善可能与肝脲原性增强作为糖尿引起的体液损失的代偿性保水机制有关。

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引用次数: 0

Neuron-specific overexpression of human vasoactive intestinal peptide receptor 2 in mice causes cognitive dysfunction and abnormal dendritic morphology in the prefrontal cortex 人类血管活性肠肽受体2在小鼠神经元特异性过表达导致认知功能障碍和前额叶皮层树突形态异常

IF 2.9 3区医学 Q2 PHARMACOLOGY & PHARMACY

Journal of pharmacological sciences

Pub Date : 2025-12-16 DOI: 10.1016/j.jphs.2025.12.005

Ami Ono , Tatsunori Miyaoka , Daichi Koan , Zihao Jin , Lu Chen , Atsuko Hayata-Takano , Satoshi Asano , Rei Yokoyama , Kenji Ishimoto , Nobumasa Hino , Akihiro Harada , Takanobu Nakazawa , Hitoshi Hashimoto , James A. Waschek , Shinsaku Nakagawa , Kotaro Tanimoto , Yukio Ago

Accumulating evidence suggests that microduplications of the VIPR2 gene are strongly associated with schizophrenia. VIPR2 encodes vasoactive intestinal peptide receptor 2 (VPAC2). However, cell-type-specific actions of VPAC2 overexpression with respect to schizophrenia remain unclear. Therefore, we aimed to determine the effects of human VPAC2 overexpression in neurons on cognition-related behaviors and prefrontal cortex dendritic morphology in mice. We crossed a Tau-Cre mouse line, which targets neuronal recombinase activity, with a newly generated double transgenic mouse line containing tetracycline-responsive element-human VPAC2-IRES-mCherry and ROSA:LNL:tTA. Immunohistochemical and Western blot analyses revealed that VPAC2 was overexpressed in neurons throughout the brain. Mice that overexpressed VPAC2 showed impaired performance in the novel object recognition test. Furthermore, VPAC2-overexpressing mice exhibited significant reductions in brain weight and the length, branch number, and complexity of arborization of prefrontal cortex pyramidal neuron dendrites. RNA sequencing analysis revealed that VPAC2 overexpression may affect signaling pathways involved in regulating stem cell pluripotency, cell cycle, and actin cytoskeleton. Quantitative PCR analysis also confirmed increased expression of the X-linked lymphocyte-regulated 3B gene, which regulates dendritic morphogenesis and spine assembly. These results suggest that VPAC2 overexpression in neurons has a detrimental effect on brain development, which leads to impaired neural circuitry and cognitive function.

越来越多的证据表明，VIPR2基因的微复制与精神分裂症密切相关。VIPR2编码血管活性肠肽受体2 （VPAC2）。然而，VPAC2过表达对精神分裂症的细胞类型特异性作用尚不清楚。因此，我们旨在确定人类神经元中VPAC2过表达对小鼠认知相关行为和前额叶皮层树突形态的影响。我们将靶向神经元重组酶活性的Tau-Cre小鼠系与新生成的含有四环素应答元件-人VPAC2-IRES-mCherry和ROSA:LNL:tTA的双转基因小鼠系杂交。免疫组织化学和Western blot分析显示，VPAC2在全脑神经元中过表达。过表达VPAC2的小鼠在新物体识别测试中的表现受损。此外，过表达vpac2的小鼠表现出脑重量和前额皮质锥体神经元树突的长度、分支数量和树突复杂性的显著减少。RNA测序分析显示，VPAC2过表达可能影响调控干细胞多能性、细胞周期和肌动蛋白细胞骨架的信号通路。定量PCR分析也证实了x连锁淋巴细胞调节3B基因的表达增加，该基因调节树突形态发生和脊柱组装。这些结果表明，神经元中VPAC2过表达对大脑发育有不利影响，导致神经回路和认知功能受损。

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引用次数: 0

Src-dependent modulation of IFNγ-induced PD-L1 expression in human breast cancer cell lines 人乳腺癌细胞系中ifn γ-诱导的PD-L1表达的src依赖性调节

IF 2.9 3区医学 Q2 PHARMACOLOGY & PHARMACY

Journal of pharmacological sciences

Pub Date : 2025-12-16 DOI: 10.1016/j.jphs.2025.12.004

Chihiro Hayashi , Yuto Mizuno , Yu Iida , Akane Nagasako , Michiko Endo , Wakana Fukae , Eriko Yamashita , Yoshihiro Ishikawa , Masanari Umemura

Triple-negative breast cancer (TNBC), which lacks expression of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2), is associated with poor prognosis. Immune checkpoint inhibitors (ICIs) have emerged as a promising therapeutic option for TNBC, but their efficacy remains limited due to resistance. In this study, we investigated whether the non-receptor tyrosine kinase Src (Src tyrosine kinase) regulates interferon-gamma (IFNγ)-induced expression of programmed death-ligand 1 (PD-L1). IFNγ stimulation of TNBC and luminal A breast cancer cell lines induced time-dependent phosphorylation of Src at its activation site (Y419). Pharmacological inhibition of Src significantly suppressed IFNγ–induced PD-L1 mRNA and protein expression, as well as activation of PD-L1–related transcription factors, suggesting transcriptional regulation. In co-culture assays with CD8⁺ T-cells, TNBC cells were more susceptible to T-cell–mediated cytotoxicity compared with luminal A cells, and Src inhibition further enhanced this cytotoxicity. These findings indicate that Src plays a crucial role in IFNγ–mediated PD-L1 expression and immune evasion in TNBC cell lines. Src inhibition may represent a promising combinatorial strategy to enhance antitumor immunity in TNBC cell lines.

三阴性乳腺癌（TNBC）缺乏雌激素受体、孕激素受体和人表皮生长因子受体2 （HER2）的表达，预后较差。免疫检查点抑制剂（ICIs）已成为TNBC的一种有希望的治疗选择，但由于耐药性，其疗效仍然有限。在这项研究中，我们研究了非受体酪氨酸激酶Src （Src酪氨酸激酶）是否调节干扰素γ (IFNγ)诱导的程序性死亡配体1 （PD-L1）的表达。IFNγ刺激TNBC和luminal A乳腺癌细胞系诱导Src在其激活位点的时间依赖性磷酸化（Y419）。药理抑制Src可显著抑制ifn γ诱导的PD-L1 mRNA和蛋白表达，以及PD-L1相关转录因子的激活，提示有转录调控作用。在与CD8+ t细胞共培养实验中，与腔内A细胞相比，TNBC细胞更容易受到t细胞介导的细胞毒性的影响，而Src抑制进一步增强了这种细胞毒性。这些发现表明Src在TNBC细胞系中ifn γ介导的PD-L1表达和免疫逃避中起关键作用。Src抑制可能是增强TNBC细胞系抗肿瘤免疫的一种有前途的组合策略。

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引用次数: 0

Magnesium deficiency differentially modulates hippocampal and prefrontal oscillations and cardiac rhythms 镁缺乏对海马和前额叶振荡和心律的调节存在差异

IF 2.9 3区医学 Q2 PHARMACOLOGY & PHARMACY

Journal of pharmacological sciences

Pub Date : 2025-12-09 DOI: 10.1016/j.jphs.2025.12.002

Sora Inoue , Yuji Ikegaya , Nobuyoshi Matsumoto , Tetsuhiko Kashima

Magnesium (Mg) is an essential cation critical for neuronal and cardiac homeostasis, principally by modulating N-methyl-d-aspartate (NMDA) receptor function. While magnesium deficiency (MgD) is known to impair memory and autonomic function, the systemic interplay remains poorly understood.

As a preliminary step to investigating neural activity during memory tasks, this study investigated the effects of 3 weeks of MgD on neural activity patterns and cardiac function in rats. Simultaneous electrophysiological recordings from the dorsal hippocampus and medial prefrontal cortex, along with electrocardiogram and electromyogram (EMG) monitoring, revealed that MgD selectively altered neural oscillations without affecting cardiac function or sleep architecture. Notably, frequency-specific changes in local field potentials (LFPs) were most pronounced during quiet wakefulness under dark conditions. This excessive enhancement of gamma wave activity may contribute to memory impairment.

This 3-week deficiency was characterized by altered neural excitability, which could lead to cognitive impairment and partial cardiac arrhythmia.

Our findings demonstrate that spontaneous neural activity is altered even in the 3-week of MgD and support a model in which the deficiency progressively disrupts physiological regulation.

镁（Mg）是神经元和心脏稳态的重要阳离子，主要通过调节n -甲基-d-天冬氨酸（NMDA）受体的功能。虽然镁缺乏（MgD）已知会损害记忆和自主神经功能，但其系统性相互作用仍知之甚少。作为研究记忆任务期间神经活动的初步步骤，本研究调查了3周MgD对大鼠神经活动模式和心功能的影响。海马背侧和内侧前额皮质的同时电生理记录，以及心电图和肌电图（EMG）监测显示，MgD选择性地改变了神经振荡，而不影响心脏功能或睡眠结构。值得注意的是，局部场电位（LFPs）的频率特异性变化在黑暗条件下安静清醒时最为明显。这种伽马波活动的过度增强可能会导致记忆障碍。这3周的缺乏以神经兴奋性改变为特征，这可能导致认知障碍和部分心律失常。我们的研究结果表明，即使在MgD的3周内，自发神经活动也会发生改变，并支持这种缺陷逐渐破坏生理调节的模型。

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引用次数: 0

Delayed response of the median raphe serotonin neurons projecting to the ventral hippocampus to aversive stimuli 中缝正中5 -羟色胺神经元投射到腹侧海马对厌恶刺激的延迟反应

IF 2.9 3区医学 Q2 PHARMACOLOGY & PHARMACY

Journal of pharmacological sciences

Pub Date : 2025-12-08 DOI: 10.1016/j.jphs.2025.12.003

Hinako Morishita , Harune Hori , Hiroyuki Kawai , Hisashi Shirakawa , Hitoshi Hashimoto , Kazuki Nagayasu

Appropriate processing of aversive information is essential for survival. We previously demonstrated that serotonin neurons in the median raphe nucleus (MRN) play a key role in such processing; however, MRN responses to predictive cues of aversive events remain unclear. Here, we found that the MRN serotonin neurons were activated by aversive air-puff stimuli but not by auditory cues predicting the air puff. Moreover, delayed activation of the ventral hippocampus-projecting MRN serotonin neurons, together with subsequent 5-HT_2A receptor signaling, was required for aversion. These findings shed light on the roles of the hippocampus-projecting MRN serotonin neurons and elucidate their molecular mechanisms.

对厌恶信息的适当处理对生存至关重要。我们之前已经证明中缝核（MRN）中的5 -羟色胺神经元在这一过程中起关键作用；然而，MRN对厌恶事件预测线索的反应尚不清楚。在这里，我们发现MRN血清素神经元被令人厌恶的吹气刺激激活，而不是被预测吹气的听觉线索激活。此外，延迟激活腹侧海马突起的MRN 5-羟色胺神经元，以及随后的5-HT2A受体信号，是厌恶所必需的。这些发现揭示了海马投射MRN血清素神经元的作用，并阐明了它们的分子机制。

引用次数: 0

β2 microglobulin promotes pericyte proliferation through toll-like receptor 4 β2微球蛋白通过toll样受体4促进周细胞增殖

IF 2.9 3区医学 Q2 PHARMACOLOGY & PHARMACY

Journal of pharmacological sciences

Pub Date : 2025-12-04 DOI: 10.1016/j.jphs.2025.12.001

Yoshino Yonezu , Akiko Uyeda , Hidemi Misawa , Rieko Muramatsu

Pericytes are perivascular cells that contribute to maintaining vascular integrity and central nervous system homeostasis. β₂-microglobulin (B2M) is a component of the major histocompatibility complex class I molecule; it has recently been implicated in age-related and injury-associated inflammation. Here, we investigated the phenotypic and transcriptomic effects of B2M on mouse brain pericytes in vitro. B2M treatment increased Bromodeoxyuridine (BrdU) incorporation into the cultured pericytes as well as the number of Ki67-positive pericytes. Morphologically, B2M promoted pericyte extension. Toll-like receptor 4 (TLR4), one of the key molecules that regulates B2M function, was involved in the B2M-dependent pericyte proliferation. These findings were consistent with RNA-seq results showing differential expression of genes related to cell proliferation. These results suggest that B2M directly acts on pericytes and regulates part of their functional responses through TLR4 signaling.

周细胞是血管周围的细胞，有助于维持血管完整性和中枢神经系统的稳态。β2-微球蛋白（B2M）是主要组织相容性复合体I类分子的组成部分；它最近被认为与年龄相关和损伤相关的炎症有关。在此，我们在体外研究了B2M对小鼠脑周细胞的表型和转录组效应。B2M处理增加了培养周细胞中溴脱氧尿苷（BrdU）的掺入以及ki67阳性周细胞的数量。形态学上，B2M促进周细胞扩展。toll样受体4 （Toll-like receptor 4, TLR4）是调控B2M功能的关键分子之一，参与B2M依赖性周细胞增殖。这些发现与RNA-seq结果一致，显示与细胞增殖相关的基因的差异表达。这些结果表明B2M直接作用于周细胞，并通过TLR4信号通路调控其部分功能反应。

引用次数: 0

Constituents of essential oils as modulators of TRP channels: Focus on cognitive functions, neurodegenerative, and psychological diseases 精油作为TRP通道调节剂的成分：关注认知功能，神经退行性疾病和心理疾病

IF 2.9 3区医学 Q2 PHARMACOLOGY & PHARMACY

Journal of pharmacological sciences

Pub Date : 2025-12-02 DOI: 10.1016/j.jphs.2025.11.007

Olesia F. Moroz , Viktoriia I. Kravchenko , Alexander V. Zholos

Essential oils have long been recognized for their therapeutic potential, with growing interest in their molecular mechanisms of action in neurological health. Among emerging targets, polymodal Ca²⁺-permeable Transient Receptor Potential (TRP) cation channels have gained particular attention for their roles in neuronal signaling, synaptic plasticity, and modulation of cognitive, neurodegenerative, and psychological disorders. This review explores the ability of essential oil constituents to modulate TRP channels. The major channels to be discussed here include TRPV1, TRPM8, and TRPA1 and some other TRPVs and TRPMs. Some TRPC members have also been reviewed, albeit more briefly. Key bioactive compounds – including menthol, linalool, and eugenol – are highlighted for their ability to interact with TRP channels, while influencing neurophysiological pathways related to learning, memory, neuroinflammation, and emotional regulation. Preclinical evidence suggests these interactions may offer neuroprotective, anxiolytic, and antidepressant effects. However, challenges such as bioavailability, standardization, and safety remain barriers to clinical translation. This review underscores the therapeutic promise of essential oil constituents as modulators of TRP channels and outlines future directions for their integration into neurotherapeutic strategies.

长期以来，人们一直认识到精油的治疗潜力，人们对其在神经系统健康中的分子作用机制越来越感兴趣。在新兴的靶点中，多模态Ca2+可渗透的瞬时受体电位（TRP）阳离子通道因其在神经元信号传导、突触可塑性以及认知、神经退行性和心理障碍的调节中的作用而受到特别关注。本文综述了精油成分调节TRP通道的能力。这里讨论的主要通道包括TRPV1、TRPM8、TRPA1以及其他一些trpv和trpm。一些TRPC成员也接受了审查，尽管比较简短。关键的生物活性化合物——包括薄荷醇、芳樟醇和丁香酚——因其与TRP通道相互作用的能力而被强调，同时影响与学习、记忆、神经炎症和情绪调节相关的神经生理途径。临床前证据表明，这些相互作用可能具有神经保护、抗焦虑和抗抑郁作用。然而，诸如生物利用度、标准化和安全性等挑战仍然是临床翻译的障碍。这篇综述强调了精油成分作为TRP通道调节剂的治疗前景，并概述了它们整合到神经治疗策略的未来方向。

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引用次数: 0

RNA-mediated aggregation mechanism of prion-like proteins and its application to drug discovery 朊病毒样蛋白的rna介导聚集机制及其在药物发现中的应用

IF 2.9 3区医学 Q2 PHARMACOLOGY & PHARMACY

Journal of pharmacological sciences

Pub Date : 2025-11-29 DOI: 10.1016/j.jphs.2025.11.006

Yasushi Yabuki , Norifumi Shioda

Neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease are on the rise in super-aging societies. However, the mechanisms underlying the aggregation and propagation of prion-like proteins such as α-synuclein and Tau that contribute to the pathogenesis of neurodegeneration remain poorly understood. Although prion-like proteins are known to undergo liquid–liquid phase separation (LLPS) followed by a sol–gel transition in vitro, the key factors governing their phase transition remain to be elucidated in vivo. Most prion-like proteins are classified as RNA-binding proteins, and recent studies suggest that RNA plays a critical role in mediating both LLPS and the subsequent sol–gel transition of these proteins. In the review, we summarized our findings on RNA G-quadruplexes (rG4s) as a pathological key molecule in neurodegenerative disorders and introduce recent advances in RNA-induced phase transition of prion-like proteins.

神经退行性疾病，如阿尔茨海默病和帕金森病，在超老龄化社会中呈上升趋势。然而，朊病毒样蛋白（如α-突触核蛋白和Tau）聚集和繁殖的机制仍不清楚，这些蛋白与神经变性的发病机制有关。虽然已知朊病毒样蛋白在体外经历液-液相分离（LLPS），然后是溶胶-凝胶转变，但控制其相变的关键因素仍有待于在体内阐明。大多数朊病毒样蛋白被归类为RNA结合蛋白，最近的研究表明RNA在介导LLPS和随后的这些蛋白的溶胶-凝胶转化中起着关键作用。本文综述了RNA g -四重复合物（rG4s）作为神经退行性疾病病理关键分子的研究进展，并介绍了RNA诱导朊蛋白样蛋白相变的最新进展。

引用次数: 0