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更新于：2025-05-07

CRYAA

更新于：2025-05-07

基本信息

别名

Alpha-crystallin A chain、Alpha-crystallin A(1-162)、Alpha-crystallin A(1-168)

+ [6]

简介

Contributes to the transparency and refractive index of the lens (PubMed:18302245). In its oxidized form (absence of intramolecular disulfide bond), acts as a chaperone, preventing aggregation of various proteins under a wide range of stress conditions (PubMed:18199971, PubMed:19595763, PubMed:22120592, PubMed:31792453). Required for the correct formation of lens intermediate filaments as part of a complex composed of BFSP1, BFSP2 and CRYAA (PubMed:28935373).

关联

项与 CRYAA 相关的药物

VP1-001

靶点

CRYAA

作用机制

CRYAA调节剂

在研机构

Viewpoint Therapeutics, Inc.

原研机构

Viewpoint Therapeutics, Inc.

在研适应症

白内障 [+1]

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

US20240327439

专利挖掘

靶点

CRYAA x TTR

作用机制-

在研机构

Plex Pharmaceuticals, Inc.

原研机构

Plex Pharmaceuticals, Inc.

在研适应症

眼部疾病 [+1]

非在研适应症-

最高研发阶段药物发现

首次获批国家/地区-

首次获批日期1800-01-20

TBA-61

靶点

CRYAA

作用机制

CRYAA inhibitors

在研机构-

原研机构

Finlay Institute of Cuba

在研适应症-

非在研适应症

结核

最高研发阶段无进展

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 CRYAA 相关的临床结果

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100 项与 CRYAA 相关的转化医学

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0 项与 CRYAA 相关的专利（医药）

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1,287

项与 CRYAA 相关的文献（医药）

2025-07-01·Archives of Biochemistry and Biophysics

The p.K90N mutation in human HSPB5 highlights the critical role of lysine 90 in chaperone function and structural integrity

Article

作者: Moosavi-Movahedi, Ali Akbar ; Yousefi, Reza ; Stroylova, Yulia Y ; Saboury, Ali Akbar ; Shahsavani, Mohammad Bagher ; Somee, Leila Rezaei ; Amanlou, Massoud ; Mirzaei, Zahra ; Habibi-Rezaei, Mehran ; Muronetz, Vladimir I ; Ghaffari, Ahmad Reza ; Barinova, Ksenia V

HSPB5 (αB-crystallin), a small heat shock protein, stabilizes proteins and prevents misfolded protein aggregation through dynamic oligomer formation. Mutations in HSPB5 can result in diseases such as myopathy and cataracts. This study focuses on the myopathy-associated p.K90N mutation in the α-crystallin domain and its impact on the structure and function of human HSPB5. The recombinant mutated protein was expressed and purified for analysis using spectroscopy, microscopy, and molecular dynamics simulations. Our results reveal that the p.K90N mutation induces significant structural alterations, including an increase in β-sheet content and a reduction in α-helical structure compared to the wild-type protein. Molecular dynamics simulations showed an increased angle between dimers and decreased accessible surface area in the mutant protein. Additionally, the mutant exhibited a higher propensity for forming larger oligomers and amyloid fibrils, and enhanced thermal stability. These structural changes lead to reduced chaperone activity and impaired protein aggregation prevention, likely contributing to cell death and myopathy. Overall, the p.K90N mutation significantly alters the structural and functional properties of HSPB5, highlighting its pathogenic role and providing insights into disease mechanisms.

2025-05-01·International Journal of Biological Macromolecules

Impact of crowding on aggregation of UV-irradiated βL-crystallin and chaperone like activity of α-crystallin depends of the nature of a crowding agent

Article

作者: Muranov, Konstantin O ; Poliansky, Nikolay B ; Borzova, Vera A

The effect of crowding on the aggregation of UV irradiated β_L-crystallin and the chaperone-like activity of α-crystallin has been studied. PEG-20000, BSA and γ-crystallin were used as crowders. It was shown that the initial rate of aggregation of UV irradiated β_L-crystallin depended on the type of crowder: the rate did not change in the presence of BSA, doubled when the concentration of γ-crystallin reached 30 mg/ml, and increased linearly with increasing PEG concentration. It was found that PEG is not an inert compound, but causes additional destabilization and denaturation of UV irradiated β_L-crystallin. The nucleation time of UV irradiated β_L-crystallin aggregation in the presence of BSA and γ-crystallin decreased linearly with an increase in the excluded volume up to 5 %, then remained constant. It was found that BSA and γ-crystallin reduced the initial adsorption capacity of α-crystallin, which was used to quantify chaperone-like activity, in a concentration-dependent manner. g-crystallin demonstrated a greater ability to suppress chaperone-like activity compared to BSA. This difference is due to γ-crystallin ability to interact with α-crystallin. The obtained results indicate the importance of using the exact same crowders that in vivo create the environment of the biochemical process for study in vitro.

2025-05-01·Ophthalmology and Therapy

Comprehensive Analysis of Congenital Aniridia and Differential Diagnoses: Genetic Insights and Clinical Manifestations

Review

作者: Suiwal, Shweta ; Stachon, Tanja ; Szentmáry, Nóra ; Obst, Jessica ; Hall, Jonathan ; Jávorszky, Eszter ; Corton, Marta ; Maka, Erika ; Amini, Maryam ; Seitz, Berthold ; Waizel, Maria Della Volpe ; Fries, Fabian Norbert ; Tory, Kálmán ; Grünauer-Kloevekorn, Clara

INTRODUCTIONCongenital aniridia (CA) is a severe and complex disorder involving the entire eye, primarily characterized by iris anomalies alongside other clinical features that pose significant risks to vision. This study seeks to offer a comprehensive overview of CA by detailing its clinical presentations, genetic underpinnings, associated phenotypes, and differential diagnoses. Additionally, it proposes a diagnostic framework to distinguish CA from other conditions that present with similar iris abnormalities.METHODSWe conducted a comprehensive literature review to compile and analyze clinical and genetic data related to CA and its differential diagnoses. We included all studies describing the clinical characteristics, pathogenic variants, and associated syndromes of congenital aniridia.RESULTSCA presents a wide range of ocular symptoms. Pathogenic variants in the PAX6 gene are the primary genetic cause of CA, though variations in other genes, including FOXC1, PITX2, CYP1B1, FOXD3, PITX3, CPAMD8, ITPR1, TENM3, TRIM44, COL4A1, CRYAA, and PXDN may also be implicated. The differential diagnosis of CA requires careful consideration of conditions with overlapping symptoms, such as WAGR syndrome (which involves deletions affecting the PAX6 and WT1 genes on chromosome 11p13, and potentially BDNF on 11p14.1), Axenfeld-Rieger syndrome (FOXC1/PITX2), ring-chromosome 6 syndrome (which involves FOXC1 microdeletion), COL4A1-related anterior segment dysgenesis, Gillespie syndrome (ITPR1 gene) or Peters anomaly. Accurate diagnosis can be achieved by evaluating specific clinical features-including iris anomalies, aniridia-associated keratopathy, cataracts, glaucoma, foveal hypoplasia, nystagmus, and optic nerve head abnormalities-supplemented by genetic testing.CONCLUSIONSUnderstanding the diverse clinical presentations and genetic basis of diseases associated with iris abnormalities is essential for accurate diagnosis and effective management. Integrating genetic diagnostics into the evaluation process enables the development of tailored treatment strategies, which can significantly improve patient outcomes.

项与 CRYAA 相关的新闻（医药）

2024-08-20

·赛柏蓝

30分钟起效、维持10小时，一老花眼药物递交上市申请

编者按：本文来自药渡，作者四月的雨；赛柏蓝授权转载，编辑相宜 01 30分钟快速起效有效时间达10小时近日，Lenz向FDA递交了老花眼新药醋克利定（Aceclidine）的上市申请，该药30分钟即可起效，有效时间达10小时。醋克利定是一种小分子乙酰胆碱受体激动剂，其主要靶点为mAChRs，主要用于治疗眼部疾病和神经系统疾病。目前在研的适应症包括老花眼、瞳孔缩小和近视。该药的原研机构为Lenz Therapeutics，目前在全球的研发状态是申请上市，而在中国的最高研发状态为临床3期。醋克利定作为一种针对mAChRs的治疗药物，有望为眼部疾病和神经系统疾病的患者带来新的治疗选择。随着药物的研发进展，其上市后将可能为患者提供更多治疗的可能性，对于相关领域的患者具有一定的临床意义。效果方面，醋克利定具有起效快以及效果持久的优点。临床3期数据显示，71%患者在30分钟内实现视力表上三行或更大的改善，40％的患者在10小时内实现了视力表上三行或更多的改善。近距离最佳矫正视力（BCDVA）显著提高了三行（15个字母）或更多，同时远距离视力却没有下降一行（5个字母）或更多，LENZ报告了关键性3期研究的积极顶线数据。LNZ100（1.75% Aceclidine）达到了所有主要和次要近视力改善终点。 02 全球在研老花眼药物盘点据统计，当前全球共有多款老花眼在研药物，但大多处于早期开发阶段，下表为当前全球在研药物信息汇总。表1. 部分老花眼全球在研药物当前老视适应症临床前阶段有8种药物，临床3期有4种药物，临床2期有2种药物，临床1期有3种药物，申请上市有2种药物。值得注意的是，已经有1种药物处于批准上市阶段，即盐酸毛果芸香碱，表明该赛道具有较高的可行性。但是目前该赛道在临床申请批准和临床3期阶段的药物数量相对较少，需要加强研发力度，以提高新药上市的成功率。表2. 老视适应症研发阶段药物数量汇总，来源：药渡数据在研企业方面，其中大多数药物来自中小型公司，如Visus Therapeutics, Inc.以及Cytokinetics, Inc.等，但也有Lenz Therapeutics, Inc.和Zhaoke Ophthalmology Ltd.等较大的药企参与，数据显示，当前已有20余家药企参与了相关药物的研发。靶点方面，包括mAChRs、α2A-AR、ADRA2xmAChRs和CRYAA在内的多个靶点。其中，有1个药物针对mAChRs已经申请上市，1个针对α2A-AR和ADRA2x mAChRs的药物处于临床3期阶段，而针对CRYAA的药物还处于临床前阶段。因此，针对这些靶点的药物仍处于不同的研发阶段，且有望在未来为相关疾病的治疗做出贡献。综合分析表明，老花眼当前研发药物具有多款，且处于不同研发阶段的药物分布相对均衡。药物类型方面，目前老花眼在研药物基本为小分子化药，期待其他类药物在未来应用于该赛道。总体来讲，当前全球老花眼在研药物处于临床前阶段的药物数量最多，共计8种，临床1期、临床2期、临床3期以及申请上市的药物相比于临床前阶段在研药物数量偏少，分别是3种、2种、4种和2种。具体到机构的药物研发数量分布来看，以Visus Therapeutics, Inc.、Cellix Bio Pvt Ltd.和Cloudbreak Pharma, Inc.为代表的多家机构在临床前阶段有着较多的在研药物。此外，从国家/地区维度来看，中国药企也积极布局该赛道，有12家研发机构进行布局。在药物类型分布方面，小分子化药占据着绝对主导地位，涉及的研发阶段包括临床前、临床申请批准、临床3期和申请上市。综上所述，当前该药物研发领域存在着以下机会和挑战：在机构布局上，中国作为全球重要的制药市场，具备着较大的研发优势；在研发阶段上，临床前和临床3期处于较为活跃的状态，尤其是针对老花眼等疾病的研发；在药物类型上，小分子化药的研发较为活跃。然而也面临着国外制药企业技术实力雄厚、研发条件优越的竞争挑战。因此，国内制药企业应加强自主创新，提高研发实力，同时利用国内市场优势，加强国际合作，提升整体竞争力。 03 老花眼患者基数庞大相关药物市场空间广阔根据WHO发布的《World report on vision（2019）》，2015年全球共有18亿人患有老花眼，其中包括8.26亿未治愈，预计到2020年，老花眼患病数量将增加到21亿人。根据《2023中国老花眼人群洞察报告》，我国35岁以上的人口中，有老花眼问题人群占比56.9%，达3.9亿人，由此可见，老花眼赛道存在庞大的潜在药物市场，潜在市场规模大约为280亿美金。图1.全球不同地区老花眼患者总人数及未治愈人数占比（单位：百万人）来源：WHO、太平洋证券而随着我国人口老龄化的加剧，未来老花眼人数会持续升高，我国老花眼患者急需新的治疗方法的出现。 04 小结老花眼主要是由于晶状体的正常适应性丧失，睫状肌功能下降，从而使视线不能集中于手臂距离以上的目标。这种疾病随着年龄增加愈发严重，大约在四十岁左右就会出现，六十五岁以后就会逐渐丧失聚焦能力。随着老花眼新药醋克利定向FDA递交上市申请，意味着滴眼药水治疗老花眼的时代即将来临。但是我国老龄化速度加快，老花眼人群庞大，国内目前尚无老花眼药物获批，期待未来涌现出新的老花眼治疗药物。 END 内容沟通：郑瑶（13810174402）医药代理商产品交流群扫描下方二维码加入银发经济市场机遇交流群扫描下方二维码加入左下角「关注账号」，右下角「在看」，防止失联

临床3期临床2期临床结果上市批准临床成功