瑞金药师讲用药｜AI文献抓取｜药学基础研究· 精选回顾
药学基础研究· 精选回顾
【AI文献抓取】为药学人员提供最新的科研进展，作为各自研究方向参考。本期为「药学基础研究」栏目精选回顾。按批次、期刊、研究范式3个维度，精选出2篇代表性成果，供集中回顾
期待“瑞金药师讲用药”的这一栏目对您的科研工作有帮助！
▎本期目录 · Contents
1. 神经退行性病变的本质：神经免疫对话失衡与免疫治疗新策略
Neurodegeneration as a dysregulation of neuroimmune crosstalk.
2. PROTAC里程碑：vepdegestrant获批治疗ESR1突变乳腺癌
The PROTAC milestone: FDA approval of vepdegestrant (ARV-471) for ESR1-mutated breast cancer.
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▎综述·Reviews
Neurodegeneration as a dysregulation of neuroimmune crosstalk.
Cell 丨 2026-08 丨 Review
▍神经退行性病变的本质：神经免疫对话失衡与免疫治疗新策略
研究背景
传统观点认为神经退行性疾病（如阿尔茨海默病、帕金森病）是神经元内在病变所致，但越来越多的证据表明其本质是神经系统与免疫系统之间对话的崩溃。免疫细胞并非被动的旁观者，而是神经元可塑性与修复能力的哨兵和塑造者。本文系统提出，神经退行性病变是一种神经免疫对话失调，保护性信号丢失而适应不良反应占据主导。
核心发现
• 提出神经退行性病变是神经免疫对话失衡的新框架，免疫系统既是脑健康的传感器也是驱动器
• 系统整合了神经科学、免疫学与表观遗传学证据，阐明免疫细胞与炎症信号在全生命周期中对脑功能的塑造作用
• 提出恢复免疫稳态、精细调控炎症反应、靶向免疫状态表观遗传调节剂三大干预方向
• 明确指出免疫疗法有望不仅延缓退行进展，还可促进神经功能恢复
领域意义
该综述将神经退行性疾病的治疗从单纯神经元保护拓展至神经免疫网络调控，为阿尔茨海默病、帕金森病等开发免疫靶向疗法提供了全新思路。小胶质细胞替换、抗炎信号调节及表观遗传免疫调控等方向有望转化为新一代神经退行性疾病治疗策略。
英文摘要 (Abstract)
Neurodegeneration is increasingly recognized not only as a disorder of neurons but also as a breakdown of dialogue between the nervous and immune systems. Recent discoveries reveal that immune cells and inflammatory signals are deeply interwoven with brain function across the lifespan. Far from passive responders, immune cells act as sentinels and shapers of neuronal resilience, vulnerability, and repair. Together, robust data support a model in which neurodegeneration emerges from complex interactions between neural and immune networks, positioning the immune system as both a sensor and driver of brain health. This perspective synthesizes a growing body of work arguing that neurodegenerative diseases are a failure of neuroimmune crosstalk-where protective signals are lost, and maladaptive responses take hold. By restoring immune homeostasis, fine-tuning inflammatory responses, or targeting epigenetic regulators of the immune state, it may be possible not only to slow degeneration but also to promote recovery. We outline the key challenges and opportunities for this paradigm shift and highlight how a deeper integration of neuroscience and immunology could transform the future of treating neurodegenerative diseases. Lastly, we describe critical focus areas to improve our understanding of neurodegeneration and highlight the development of immune-based therapeutics for neurodegeneration.
DOI: 10.1016/j.cell.2026.07.015
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The PROTAC milestone: FDA approval of vepdegestrant (ARV-471) for ESR1-mutated breast cancer.
Drug Discov Today 丨 2026-08 丨 Review
▍PROTAC里程碑：vepdegestrant获批治疗ESR1突变乳腺癌
研究背景
靶向蛋白降解（TPD）是近年药物发现领域最具变革性的技术之一，通过诱导E3连接酶与靶蛋白接近实现催化性降解。尽管PROTAC在临床前研究中展现出巨大潜力，但长期缺乏获批药物来验证这一模式。vepdegestrant（ARV-471）作为一款口服ERα靶向PROTAC的获批，成为该领域的历史性转折点。
核心发现
• 2026年FDA批准vepdegestrant（ARV-471）用于ESR1突变乳腺癌，成为首个获批的PROTAC药物
• 与占据驱动的选择性雌激素受体降解剂不同，vepdegestrant通过催化性招募CRBN E3连接酶诱导ERα泛素化并降解
• III期VERITAC-2试验显示，在ESR1突变内分泌耐药乳腺癌中，vepdegestrant较氟维司群显著改善无进展生存期
• 该批准验证了PROTAC作为治疗平台的成药性，重新定义口服超越类药五规则（beyond-Rule-of-5）的设计原则
领域意义
该里程碑标志着靶向蛋白降解技术从概念走向临床获批，为诱导邻近性药物（induced-proximity medicines）开辟了新前沿。它将推动更多过去被认为不可成药的靶点采用降解策略开发，并激励分子胶等邻近诱导模式药物的研发。
英文摘要
The 2026 FDA approval of vepdegestrant (ARV-471), an oral proteolysis-targeting chimera (PROTAC) that targets the estrogen receptor α (ERα), represents a historic milestone for targeted protein degradation. Unlike selective estrogen receptor degraders that operate via occupancy-driven destabilization, vepdegestrant catalytically recruits the CRBN E3 ligase to ERα, inducing its ubiquitination and proteasomal degradation. In the Phase III VERITAC-2 trial, vepdegestrant significantly improved progression-free survival versus fulvestrant in ESR1-mutated, endocrine-resistant breast cancer. This milestone approval validates the PROTAC modality as a therapeutic platform, redefining oral beyond-Rule-of-5 design principles and opening new frontiers for induced-proximity medicines.
DOI: 10.1016/j.drudis.2026.104772
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▎参考文献·References
[1] Neurodegeneration as a dysregulation of neuroimmune crosstalk. Cell. 2026 (2026-08). DOI: 10.1016/j.cell.2026.07.015 https://doi.org/10.1016/j.cell.2026.07.015
[2] The PROTAC milestone: FDA approval of vepdegestrant (ARV-471) for ESR1-mutated breast cancer. Drug Discov Today. 2026 (2026-08). DOI: 10.1016/j.drudis.2026.104772 https://doi.org/10.1016/j.drudis.2026.104772
初稿、编辑：许倍铭
原标题：《瑞金药师讲用药｜AI文献抓取｜药学基础研究· 精选回顾》