2. Academic Validation
  3. Lysosome targeting fluorescent probe for NAAA imaging and its applications in the drug development for anti-inflammatory

Lysosome targeting fluorescent probe for NAAA imaging and its applications in the drug development for anti-inflammatory

  • Int J Biol Macromol. 2024 Apr;263(Pt 2):130307. doi: 10.1016/j.ijbiomac.2024.130307.
Limin Zhou 1,  Manman Tian 2,  Baojing Zhang 2,  Xudong Cao 3,  Xiaokui Huo 2,  Fangyu Yang 4,  Peng Cao 5,  Lei Feng 6,  Xiaochi Ma 2,  Xiangge Tian 7
Affiliations

Affiliations

  • 1 Second Affiliated Hospital, Dalian Medical University, Dalian 116023, China; Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou 221004, China.
  • 2 Second Affiliated Hospital, Dalian Medical University, Dalian 116023, China.
  • 3 Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou 221004, China.
  • 4 General Hospital of Northern Theater Command, Department of Neurosurgery, Shenyang, China.
  • 5 General Hospital of Northern Theater Command, Department of Neurosurgery, Shenyang, China. Electronic address: Pengcao518@163.com.
  • 6 Second Affiliated Hospital, Dalian Medical University, Dalian 116023, China; School of Chemistry and Chemical Engineering, Henan Normal University, Xinxiang 453007, China. Electronic address: leifeng@dmu.edu.cn.
  • 7 Second Affiliated Hospital, Dalian Medical University, Dalian 116023, China. Electronic address: tianxiangge1990@163.com.
PMID: 38382784 DOI: 10.1016/j.ijbiomac.2024.130307
Abstract

N-acylethanolamine acid amidase (NAAA) is a nucleophilic lysosomal cysteine hydrolase, which primarily mediates the hydrolytic inactivation of endogenous palmitoylethanolamide (PEA), which further influences the inflammatory process by regulating peroxisome proliferator-activated receptor-α (PPAR-α). Herein, a novel lysosome (Lyso)-targeting fluorescent probe (i.e., PMBD) was designed and synthesized for detecting endogenous NAAA selectively and sensitively, allowing real-time visual monitoring of endogenous NAAA in living cells. Moreover, PMBD can target Lyso with a high colocalization in Lyso Tracker. Finally, a high-throughput assay method for NAAA inhibitor screening was established using PMBD, and the NAAA-inhibitory effects of 42 anti-inflammatory Traditional Chinese medicines were evaluated. A novel potent inhibitor of NAAA, ellagic acid, was isolated from Cornus officinalis, which can suppress LPS-induced iNOS upregulation and NO production in RAW264.7 cells that display anti-inflammatory activities. PMBD, a novel Lyso-targeting fluorescent probe for visually imaging NAAA, could serve as a useful molecular tool for exploring the physiological functions of NAAA and drug development based on NAAA-related diseases.

Keywords

Anti-inflammatory; Fluorescent probe; High-throughput screening inhibitors; Lysosome targeting; N-acylethanolamine acid amidase.

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