Cell Stress & Chaperones最新文献

英文中文

Melatonin ameliorates heat stress-induced oxidative apoptosis in mouse spermatocytes via autophagy and ferroptosis pathways 褪黑素通过自噬和铁下垂途径改善热应激诱导的小鼠精细胞氧化凋亡

IF 3.3 3区生物学 Q3 CELL BIOLOGY

Cell Stress & Chaperones

Pub Date : 2025-04-20 DOI: 10.1016/j.cstres.2025.100078

Yi-Ping Lei, Jia Wang, Peng-Luo Yin, Hua Jia, Wen-Zhi Ma

Testicular heat stress is a critical factor contributing to male infertility, with spermatocytes exhibiting heightened sensitivity to temperature elevation. This study systematically elucidates the protective mechanisms of melatonin against heat stress-induced spermatocyte injury. In a murine heat stress model, melatonin intervention significantly reduced testicular accumulation of malondialdehyde (MDA) induced by heat stress, enhanced the activities of catalase (CAT) and superoxide dismutase (SOD), and suppressed germ cell apoptosis by downregulating the pro-apoptotic protein Bax and upregulating GPX4 expression. Sycp3 immunohistochemistry demonstrated that melatonin significantly improved spermatocyte structural integrity. In the GC-2spd (ts) spermatocyte cell line model, melatonin treatment markedly reduced MDA levels and alleviated heat stress-induced oxidative apoptosis and proliferation inhibition by downregulating key apoptotic proteins (Bax, Caspase-3, and cleaved-Caspase-3). Mechanistic studies revealed that melatonin restores autophagic balance by modulating the expression of autophagy-related proteins LC3-I, LC3-II, and P62. Concurrently, melatonin downregulated ferroptosis markers P53 and COX2, inhibiting ferroptosis by blocking DNA damage response and inflammatory amplification pathways. Melatonin synergistically maintained cellular redox homeostasis by downregulating the NRF2/HO-1 pathway and upregulating GPX4 expression, significantly reducing Fe²⁺ accumulation and ameliorating iron metabolism dysregulation. This study unveils the molecular mechanisms by which melatonin mitigates testicular heat stress injury through a multitarget regulatory network, providing novel therapeutic strategies for clinical intervention in heat stress-associated infertility.

睾丸热应激是导致男性不育的一个关键因素，精子细胞对温度升高表现出更高的敏感性。本研究系统地阐明了褪黑素对热应激诱导的精母细胞损伤的保护机制。在小鼠热应激模型中，褪黑激素干预可显著降低热应激诱导的睾丸丙二醛（MDA）积累，增强过氧化氢酶（CAT）和超氧化物歧化酶（SOD）活性，并通过下调促凋亡蛋白Bax和上调GPX4表达抑制生殖细胞凋亡。Sycp3免疫组化显示褪黑素显著改善精母细胞结构完整性。在GC-2spd （ts）精细胞系模型中，褪黑素处理通过下调关键凋亡蛋白（Bax、Caspase-3和cleaved-Caspase-3），显著降低MDA水平，减轻热应激诱导的氧化性凋亡和增殖抑制。机制研究表明，褪黑素通过调节自噬相关蛋白LC3-I、LC3-II和P62的表达来恢复自噬平衡。同时，褪黑素下调铁下垂标志物P53和COX2，通过阻断DNA损伤反应和炎症扩增途径抑制铁下垂。褪黑素通过下调NRF2/HO-1通路和上调GPX4表达，协同维持细胞氧化还原稳态，显著减少Fe +积累，改善铁代谢失调。本研究揭示了褪黑素通过多靶点调控网络减轻睾丸热应激损伤的分子机制，为临床干预热应激相关性不孕提供了新的治疗策略。

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引用次数: 0

Amyloidogenesis promotes HSF1 activity enhancing cell survival during breast cancer metastatic colonization 淀粉样蛋白形成促进HSF1活性，增强乳腺癌转移定殖过程中的细胞存活。

IF 3.3 3区生物学 Q3 CELL BIOLOGY

Cell Stress & Chaperones

Pub Date : 2025-03-25 DOI: 10.1016/j.cstres.2025.03.003

Natasha Hockaden , Gabi Leriger , John Wang , Haimanti Ray , Sunandan Chakrabarti , Nicholas Downing , Jacob Desmond , David Williams , Peter C. Hollenhorst , Gregory Longmore , Richard L. Carpenter

Breast cancer is the most commonly diagnosed cancer among women and the second leading cause of cancer deaths in women. A majority of these breast cancer deaths are due to metastasis, which occurs when primary tumor cells invade into the blood stream to travel and colonize at distant organ sites. Metastatic colonization is the rate-limiting step of metastasis. Heat shock factor 1 (HSF1) is a transcription factor that has been shown to be involved in promoting malignancy with a function in metastatic dissemination due to its contribution to promoting epithelial-to-mesenchymal transition. The role of HSF1 in colonization is unclear. In this study, we observed that HSF1 was essential for metastatic colonization. Consistent with these findings, we also observed that HSF1 was more active in human metastatic tumors compared to primary tumors. HSF1 was also seen to be activated during in vitro colony formation, which was accompanied by increases in amyloid beta (Aβ) fibrils, which was also observed in human metastatic tumors. Aβ fibrils led to HSF1 activation and depletion or inhibition of HSF1 led to increases in Aβ fibrils. HSF1 inhibition with small molecule inhibitors suppressed in vitro colony formation and mammosphere growth of metastatic breast cancer cells. These results suggest that colonization increases Aβ fibril formation that subsequently activates HSF1 as a cell survival mechanism that is essential for metastatic initiation and outgrowth.

乳腺癌是妇女中最常见的癌症，也是妇女癌症死亡的第二大原因。大多数乳腺癌死亡是由于转移，当原发肿瘤细胞侵入血流并迁移到远处的器官部位时就会发生转移。转移定殖是转移的限速步骤。热休克因子1 （HSF1）是一种转录因子，由于其促进上皮-间质转化（EMT）的作用，已被证明参与促进恶性肿瘤的转移传播。HSF1在定植中的作用尚不清楚。在这项研究中，我们观察到HSF1在转移性定植中是必不可少的。与这些发现一致，我们还观察到HSF1在人类转移性肿瘤中比原发肿瘤更活跃。HSF1在体外集落形成过程中也被激活，这伴随着淀粉样蛋白（Aβ）原纤维的增加，这在人类转移性肿瘤中也被观察到。β原纤维导致HSF1激活，而HSF1的消耗或抑制导致β原纤维的增加。用小分子抑制剂抑制HSF1抑制转移性乳腺癌细胞体外集落形成和乳腺球生长。这些结果表明，定殖增加了a β纤维的形成，随后激活HSF1，这是转移起始和生长所必需的细胞存活机制。

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引用次数: 0

Lycium barbarum polysaccharide alleviates H2O2-induced premature senescence by downregulating miRNA-34a-5p in ARPE-19 cells 枸杞多糖通过下调ARPE-19细胞中的miRNA-34a-5p，缓解H2O2诱导的早衰。

IF 3.3 3区生物学 Q3 CELL BIOLOGY

Cell Stress & Chaperones

Pub Date : 2025-03-18 DOI: 10.1016/j.cstres.2025.03.002

Meng Kong , Jingwen Li , Rong Jin , Yi Zhang , Jia You , Nan Wang , Nianting Tong

The premature senescence of retinal pigment epithelium (RPE) plays a significant role in the development of age-related macular degeneration. This study aimed to investigate the potential protective effect of Lycium barbarum polysaccharide (LBP) against H₂O₂-induced premature senescence and to elucidate the underlying mechanisms. The ARPE-19 cell line was subjected to H₂O₂ exposure to create a model of premature senescence. The modulation of microRNA-34a-5p expression was accomplished using antagomir and agomir, as assessed by quantitative real-time polymerase chain reaction. The senescence model was successfully established by treating cells with 200 μM H₂O₂ for 2 hours daily over a span of three consecutive days. This oxidative stress resulted in a notable increase in the proportion of senescence-associated beta-galactosidase-positive cells, reaching 33.5%, without significant alterations in cell viability or apoptosis. In the ARPE-19 cells undergoing premature senescence, there was a marked increase in reactive oxygen species (ROS) production and malondialdehyde levels, coupled with a significant decrease in the activity of total superoxide dismutase, glutathione peroxidase, and catalase. Additionally, microRNA-34a-5p was found to be overexpressed in these cells. Treatment with LBP alleviated H₂O₂-induced premature senescence, diminished the overexpression of microRNA-34a-5p, and suppressed ROS production. Moreover, the incubation with ago-34a reversed the protective effect of LBP in ARPE-19 cells. In conclusion, the overexpression of microRNA-34a-5p contributes to the H₂O₂-induced premature senescence of ARPE-19 cells. LBP appears to mitigate this premature senescence, at least in part, by downregulating microRNA-34a-5p expression and reducing oxidative stress.

背景：视网膜色素上皮（RPE）的过早衰老在老年性黄斑变性的发生中起着重要作用。本研究旨在探讨枸杞多糖（LBP）对H2O2诱导的过早衰老的保护作用，并阐明其潜在机制：方法：将ARPE-19细胞系置于H2O2暴露下，建立早衰模型。方法：ARPE-19 细胞系暴露于 H2O2，以建立早衰模型。模型建立后，细胞在枸杞多糖存在或不存在的情况下维持。使用 antagomir 和 agomir 对 microRNA（miRNA）-34a-5p 的表达进行调节，并通过定量实时聚合酶链反应进行评估：连续三天每天用 200μM H2O2 处理细胞 2 小时，成功建立了衰老模型。这种氧化应激导致衰老相关的 beta-半乳糖苷酶阳性细胞比例明显增加，达到 33.5%，但细胞活力和凋亡没有明显变化。在过早衰老的 ARPE-19 细胞中，活性氧（ROS）生成和丙二醛（MDA）水平明显增加，同时总超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH px）和过氧化氢酶（CAT）的活性显著下降。此外，还发现 miRNA-34a-5p 在这些细胞中过度表达。用枸杞多糖处理可缓解 H2O2 诱导的早衰，减少 miRNA-34a-5p 的过表达，并抑制 ROS 的产生。此外，与 ago-34a 一起孵育可逆转枸杞多糖对 ARPE-19 细胞的保护作用：结论：miRNA-34a-5p的过表达是H2O2诱导ARPE-19细胞早衰的原因之一。枸杞多糖似乎可以通过下调 miRNA-34a-5p 的表达和减少氧化应激来缓解这种过早衰老，至少部分是这样。

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引用次数: 0

Endoplasmic reticulum stress in acute pancreatitis: Exploring the molecular mechanisms and therapeutic targets 内质网应激在急性胰腺炎：探索分子机制和治疗靶点。

IF 3.3 3区生物学 Q3 CELL BIOLOGY

Cell Stress & Chaperones

Pub Date : 2025-03-17 DOI: 10.1016/j.cstres.2025.03.001

Xiaoliang Zhang , Chenchen Xu , LiJuan Ji , Haiwei Zhang

Acute pancreatitis (AP) is associated with multiple cellular mechanisms that trigger and or are triggered by the inflammatory injury and death of the acinar cells. One of the key mechanisms is the endoplasmic reticulum (ER) stress, which manifests as an accumulation of misfolded proteins within ER, an event that has proinflammatory and proapoptotic consequences. Hence, the degree of cell insult during AP could considerably depend on the signaling pathways that are upregulated during ER stress and its resulting dyshomeostasis such as C/EBP homologous protein (CHOP), cJUN NH2-terminal kinase (JNK), nuclear factor kappa B (NF-κB), and NOD-like receptor protein 3 (NLRP3) inflammasome. Exploring these molecular pathways is an interesting area for translational medicine as it may lead to identifying new therapeutic targets in AP. This review of the literature aims to shed light on the different roles of ER stress in the etiopathogenesis and pathogenesis of AP. Then, it specifically focuses on the therapeutic implications of ER stress in this context.

急性胰腺炎（AP）与多种细胞机制有关，这些细胞机制触发或由腺泡细胞的炎症损伤和死亡触发。其中一个关键机制是内质网应激，其表现为内质网内错误折叠蛋白的积累，这一事件具有促炎症和促凋亡的后果。因此，AP过程中细胞损伤的程度可能在很大程度上取决于内质网应激过程中上调的信号通路及其导致的失衡，如C/EBP同源蛋白（CHOP）、cJUN nh2末端激酶（JNK）、核因子κB （NF-κB）和nod样受体蛋白3 （NLRP3）炎性体。对于转化医学来说，探索这些分子通路是一个有趣的领域，因为它可能导致发现新的AP治疗靶点。本文综述的目的是阐明内质网应激在AP的发病机制和发病机制中的不同作用。然后，它特别关注内质网应激在这种情况下的治疗意义。

引用次数: 0

Cover and caption 封面及标题

IF 3.3 3区生物学 Q3 CELL BIOLOGY

Cell Stress & Chaperones

Pub Date : 2025-03-01 DOI: 10.1016/S1355-8145(25)00013-6

引用次数: 0

Editorial Board Members/Copyright 编辑委员会成员/版权

IF 3.3 3区生物学 Q3 CELL BIOLOGY

Cell Stress & Chaperones

Pub Date : 2025-03-01 DOI: 10.1016/S1355-8145(25)00014-8

引用次数: 0

CHOP aggravates hepatocyte apoptosis upon endoplasmic reticulum stress by downregulating autophagy CHOP通过下调自噬，加重内质网应激下肝细胞凋亡。

IF 3.3 3区生物学 Q3 CELL BIOLOGY

Cell Stress & Chaperones

Pub Date : 2025-02-27 DOI: 10.1016/j.cstres.2025.02.005

Jia-Yu Wu , Bing Han , Ting Yang , Lu Zheng , Yi-Xin Guo , Jia-Yao Li , Xiao-Yu Guo , Huan-Huan Yin , Ru-Jia Xie

Endoplasmic reticulum (ER) stress-induced apoptosis plays a crucial role in various liver diseases. Hepatocytes respond to ER stress by activating the unfolded protein response and autophagy, which is essential for maintaining ER homeostasis. However, failure to restore ER balance via autophagy contributes to apoptosis. In this study, we aimed to explore the role of C/EBP homologous protein (CHOP) in regulating ER stress-induced apoptosis in rat hepatocytes. We found that CHOP downregulates autophagy, aggravating apoptosis. Our results revealed that inhibition of CHOP expression enhanced autophagy and reduced DTT-induced apoptosis in BRL-3A cells, whereas CHOP overexpression worsened apoptosis. Chromatin immunoprecipitation assays revealed that CHOP negatively regulates autophagy-related genes, such as ATG12, ATG5, and LC3. These findings suggest that CHOP modulation plays a crucial role in ER stress-induced hepatocyte apoptosis by regulating autophagy.

背景：与内质网（ER）应激相关的细胞凋亡涉及多种肝脏疾病，包括肝纤维化、非酒精性脂肪肝和肝硬化。肝细胞通过引发未折叠蛋白反应（UPR）和增强自噬来应对ER应激。自噬是维持ER正常功能的关键机制，它通过降解受损的ER片段和清除ER腔中的异常蛋白质聚集体来实现。如果不能通过自噬恢复ER平衡，就会对肝细胞造成危害，并导致与ER应激相关的细胞凋亡。最近的研究结果表明，C/EBP同源蛋白（CHOP）可通过下调自噬作用加剧ER应激相关的细胞凋亡，但其潜在机制仍难以确定。目的：研究CHOP对ER应激诱导的大鼠肝细胞凋亡的影响及其潜在的分子机制：方法：用雷帕霉素（RAP）和 3-甲基腺嘌呤预处理 BRL-3A 细胞，然后用二硫苏糖醇（DTT）处理。分别使用实时细胞分析（RTCA）和流式细胞仪检测细胞的生长率和凋亡率。ER应激相关分子水平通过Western印迹法测定。使用 CHOP、小干扰 RNA 和慢病毒载体系统转染 BRL-3A 细胞，观察 CHOP 基因沉默或过表达对自噬和细胞凋亡的影响。染色质免疫共沉淀（ChIP）被用来确认CHOP是否直接与ER应激下的ATG12、ATG5和LC3启动子区域结合：结果：ER应激相关分子在BRL-3A肝细胞中急剧上调，肝细胞凋亡增加。RAP 预处理明显降低了 DTT 诱导的 ER 应激相关分子的表达；相反，3-MA 预处理促进了 DTT 诱导的 ER 应激相关凋亡分子的水平。随着肝细胞中 CHOP 表达的减少，自噬相关分子的水平急剧上升，DTT 诱导的肝细胞凋亡也随之减少。然而，在过表达 CHOP 的细胞中却观察到了相反的趋势。通过 ChIP 检测发现，DTT 处理后，CHOP 对 BRL-3A 细胞中的 ATG12、ATG5 和 LC3 等自噬相关分子有负向调节作用：结论：CHOP在ER应激过程中的增强抑制了自噬，促进了肝细胞凋亡；然而，CHOP基因表达的减少可减轻DTT诱导的肝细胞凋亡。过表达 CHOP 会加重 DTT 诱导的肝细胞凋亡。

引用次数: 0

Low serum HSPA12B levels are associated with an increased risk of sarcopenia in a Chinese population of older adults 血清HSPA12B水平低与中国老年人肌肉减少症风险增加有关。

IF 3.3 3区生物学 Q3 CELL BIOLOGY

Cell Stress & Chaperones

Pub Date : 2025-02-19 DOI: 10.1016/j.cstres.2025.02.003

Xin-Feng Jiao , Yue Gao , Ran Ni , Wen-Ya Zhao , Can Zhao , Xiang Lu , Hai-Feng Zhang , Wei Gao , Lan Luo

Sarcopenia is a geriatric syndrome characterized by progressive loss of muscle mass and function. Heat shock protein (HSP) A12B is essential for angiogenesis and endothelial function. However, the association of HSPA12B levels with sarcopenia remains unclear. A total of 936 community-dwelling elderly people were recruited, and serum HSPA12B was measured by enzyme-linked immunosorbent assay. Appendicular skeletal muscle mass index (ASMI), grip strength, and gait speed were taken to assess sarcopenia. We found that serum HSPA12B levels in patients with sarcopenia (median [interquartile range] = 182.15 [137.58–225.86] ng/mL) were lower than those in elderly people without sarcopenia (228.96 [193.03–292.93] ng/mL, P < 0.001). Receiver operating characteristic curve analysis indicated that the optimal cut-off value of serum HSPA12B level for predicting sarcopenia was 185.50 ng/mL, with a sensitivity of 52.6% and a specificity of 80.8% (area under curve = 0.742, 95% confidence interval [CI] = 0.711–0.772, P < 0.001). Moreover, serum HSPA12B concentration was positively correlated with ASMI (r = 0.354, P < 0.001), grip strength (r = 0.381, P < 0.001), and gait speed (r = 0.169, P < 0.001). Multivariate logistic regression analysis showed that decreased serum HSPA12B levels (<185.50 ng/mL) were a risk factor for increased risk of sarcopenia (adjusted odds ratio = 4.335, 95% CI = 3.136–5.993, P < 0.001). In addition, serum HSPA12B level was also positively correlated with serum levels of angiogenesis markers, vascular endothelial growth factor (r = 0.080, P = 0.014), and angiopoietin-1 (r = 0.108, P = 0.001). In summary, our results indicate that low serum HSPA12B level is associated with an increased risk of sarcopenia in the elderly, suggesting a potential role of HSPA12B in the development of sarcopenia.

背景：肌肉减少症是一种以肌肉质量和功能进行性丧失为特征的老年综合征。热休克蛋白（HSP） A12B对血管生成和内皮功能至关重要。然而，HSPA12B水平与肌肉减少症的关系尚不清楚。方法：招募936名社区老年人，采用酶联免疫吸附法测定血清HSPA12B水平。采用阑尾骨骼肌质量指数（ASMI）、握力和步态速度来评估肌肉减少症。结果：我们发现，肌少症患者血清HSPA12B水平[中位数(IQR) = 182.15 (137.58-225.86) ng/mL]低于无肌少症老年人血清HSPA12B水平[228.96 (193.03-292.93)ng/mL]， P。结论：综上所述，我们的研究结果表明，血清HSPA12B水平低与老年人肌少症风险增加有关，提示HSPA12B在肌少症的发生中可能起作用。

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引用次数: 0

Increased intracellular stress responses and decreased KLF2 in adult patients with atopic dermatitis 成人特应性皮炎患者细胞内应激反应增加，KLF2降低。

IF 3.3 3区生物学 Q3 CELL BIOLOGY

Cell Stress & Chaperones

Pub Date : 2025-02-10 DOI: 10.1016/j.cstres.2025.02.001

Shuji Sugiura , Hiderou Yoshida , Hisashi Sugiura , Masami Uehara , Yasuo Sugiura , Yoshihiro Maruo , Yuji Hayashi , Takefumi Yamamoto , Takeshi Kato , Noriki Fujimoto , Jun Udagawa

Atopic dermatitis (AD) is prone to exacerbations in response to various triggering factors and flare-ups after remission. We searched for molecules associated with relapse/exacerbation of AD among molecules with altered gene expression in the skin of patients with AD. Microarray analyses were performed on lesional and nonlesional skin of adolescent or adult patients with recalcitrant AD and healthy controls. Five chaperones involved in intracellular stress responses, namely heat shock protein family A (Hsp70) member 9 (HSPA9), heat shock protein 90 beta family member 1 (HSP90B1), calnexin (CANX), malectin (MLEC; endoplasmic reticulum-associated degradation), and heat shock protein family D (Hsp60) member 1 (HSPD1), were consistently upregulated in involved and uninvolved skin of patients with AD. Damage-associated molecular patterns were upregulated in involved skin. KLF transcription factor 2 (KLF2) was decreased in involved skin and exhibited a decreasing trend in uninvolved skin of patients with AD. CD4(+)/CD8(+) double-positive cells (1.4% of T cells) were detected in lesions with declined KLF2 levels. WNT inhibitory factor 1 (WIF1) was downregulated in involved skin. Prolactin-induced protein was upregulated in only uninvolved skin of patients with AD. We found increased intracellular stress responses and decreased expression of KLF2 in the skin of patients with AD. Multifactorial genetic diseases, such as asthma, inflammatory bowel disease, type 2 diabetes, and rheumatoid arthritis, are associated with intracellular stress. Intracellular abnormalities may also be responsible for AD. Further research on AD may incorporate enhanced intracellular stress response and the decreased expression of KLF2 into the mechanism underlying AD.

特应性皮炎（AD）在缓解后容易因各种触发因素而恶化和发作。我们在阿尔茨海默病患者皮肤基因表达改变的分子中寻找与阿尔茨海默病复发/加重相关的分子。对青少年或成人顽固性AD患者和健康对照者的病变和非病变皮肤进行微阵列分析。参与细胞内应激反应的5种伴侣蛋白，即热休克蛋白家族A (Hsp70) 9号成员（HSPA9）、热休克蛋白90 β家族1号成员（HSP90B1）、calnexin （CANX）、malectin (MLEC)；内质网相关降解)和热休克蛋白家族D （Hsp60）成员1 （HSPD1）在AD患者的受累和非受累皮肤中一致上调。损伤相关的分子模式在受累皮肤中上调。KLF转录因子2 （KLF2）在AD患者受累皮肤中下降，在未受累皮肤中呈下降趋势。在KLF2水平下降的病变中检测到CD4(+)/CD8（+）双阳性细胞（占T细胞的1.4%）。WNT抑制因子1 （WIF1）在受累皮肤中下调。催乳素诱导蛋白仅在AD患者的非相关皮肤中上调。我们发现AD患者皮肤细胞内应激反应增加，KLF2表达降低。多因素遗传疾病，如哮喘、炎症性肠病、2型糖尿病和类风湿关节炎，都与细胞内应激有关。细胞内异常也可能导致AD。对AD的进一步研究可能将细胞内应激反应增强和KLF2表达降低纳入AD的机制。

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引用次数: 0

FKBP51 functions in the regulation of circadian rhythm and Alzheimer's disease FKBP51 在调节昼夜节律和阿尔茨海默病中的功能

IF 3.3 3区生物学 Q3 CELL BIOLOGY

Cell Stress & Chaperones

Pub Date : 2025-02-09 DOI: 10.1016/j.cstres.2025.02.002

Jill L. Johnson

The FK506-binding protein 51 (FKBP51) is an important regulator of glucocorticoid receptor activity and an Hsp90 cochaperone. FKBP51 has previously been identified as a drug target due to its roles in stress-related disorders and pain tolerance. Two recent publications in Cell Stress and Chaperones further explore FKBP51 functions. To understand whether FKBP51 plays a role in sleep disturbances linked to stress disorders, one study examined the role of FKBP51 in regulating the circadian rhythm. Broadening the range of Hsp90 cochaperone function, the other article summarized the role of multiple cochaperones in Alzheimer’s disease, discussing how cochaperones affect both Aβ and tau. They emphasize the role of FKBP51 in promoting tau pathogenesis and discuss the small molecule LA1011, which binds Hsp90 and competes with Hsp90-FKBP51 interaction. Further studies with LA1011 may lead to new treatments for Alzheimer’s disease and will help clarify the contributions of FKBP51 to human disorders.

fk506结合蛋白51 （FKBP51）是糖皮质激素受体活性的重要调节因子和Hsp90的合作伙伴。由于FKBP51在压力相关疾病和疼痛耐受性中的作用，它先前已被确定为药物靶点。最近发表在Cell Stress and Chaperones上的两篇文章进一步探讨了FKBP51的功能。为了了解FKBP51是否在与应激障碍相关的睡眠障碍中发挥作用，Gebru等人研究了FKBP51在调节昼夜节律中的作用。Jeanne等拓宽了Hsp90 cochaperone功能的范围，总结了多种cochaperone在阿尔茨海默病中的作用，讨论了cochaperone如何同时影响Aβ和tau。他们强调FKBP51在促进tau发病机制中的作用，并讨论了结合Hsp90并与Hsp90-FKBP51相互作用竞争的小分子LA1011。对LA1011的进一步研究可能会导致阿尔茨海默病的新治疗方法，并将有助于阐明FKBP51对人类疾病的贡献。

引用次数: 0

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