中国神经再生研究(英文版) ›› 2026, Vol. 21 ›› Issue (10): 4904-4905.doi: 10.4103/NRR.NRR-D-25-01478

• 观点:退行性病与再生 • 上一篇    下一篇

小分子髓系细胞表达的触发受体 2激动剂:从人工智能驱动发现到阿尔茨海默病的治疗应用

  

  • 出版日期:2026-10-15 发布日期:2026-06-13

Small-molecule TREM2 agonists: From artificial intelligence driven discovery to therapeutic application in Alzheimer's disease

Sungwoo Cho, Moustafa Gabr*   

  1. Department of Radiology, Molecular Imaging Innovations Institute (MI3), Weill Cornell Medicine, New York, NY, USA
  • Online:2026-10-15 Published:2026-06-13
  • Contact: Moustafa Gabr, PhD, mog4005@med.cornell.edu.
  • Supported by:
    This work was supported by the National Institutes on Aging under grant number R01AG083512 (to MG).

摘要: https://orcid.org/0000-0001-9074-3331 (Moustafa Gabr)

Abstract: The Alzheimer’s disease (AD) therapeutic landscape is evolving rapidly. While anti-amyloid antibodies have achieved regulatory approval, their incremental clinical benefits have intensified interest in neuroinflammation as a complementary therapeutic axis. Triggering receptor expressed on myeloid cells 2 (TREM2) represents a particularly attractive microglial target, given that loss-offunction variants confer a three-fold elevation in AD risk. Although TREM2 antibodies have shown promise in preclinical studies, clinical translation is hindered by fundamental limitations: restricted blood–brain barrier (BBB) penetration (< 0.1%), prohibitive annual costs exceeding $100,000, and pharmacokinetic inflexibility that precludes dose adjustment. Here, we examine how artificial intelligence (AI)-assisted approaches have enabled the discovery of small molecule TREM2 agonists and their implications for AD treatment.