2. Academic Validation
  3. Selective inhibition of monoamine oxidase B represents a therapeutic strategy for diabetic peripheral neuropathy

Selective inhibition of monoamine oxidase B represents a therapeutic strategy for diabetic peripheral neuropathy

  • Acta Pharmacol Sin. 2026 Jul;47(7):1792-1808. doi: 10.1038/s41401-026-01764-2.
Ni-Xue Song # 1,  Yan-Chun Wang # 1,  Tong Zhao # 1,  Zhi-Shuo Zhang 1,  Jia-Cheng Liu 1,  Zi-Yun Chen 1,  Yu-Jie Huang 2 3,  Jia-Ying Wang 4 5,  Xu Shen 6 7
Affiliations

Affiliations

  • 1 National Key Laboratory on Technologies for Chinese Medicine Pharmaceutical Process Control and Intelligent Manufacture, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
  • 2 National Key Laboratory on Technologies for Chinese Medicine Pharmaceutical Process Control and Intelligent Manufacture, Nanjing University of Chinese Medicine, Nanjing, 210023, China. [email protected].
  • 3 School of Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China. [email protected].
  • 4 National Key Laboratory on Technologies for Chinese Medicine Pharmaceutical Process Control and Intelligent Manufacture, Nanjing University of Chinese Medicine, Nanjing, 210023, China. [email protected].
  • 5 School of Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China. [email protected].
  • 6 National Key Laboratory on Technologies for Chinese Medicine Pharmaceutical Process Control and Intelligent Manufacture, Nanjing University of Chinese Medicine, Nanjing, 210023, China. [email protected].
  • 7 School of Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China. [email protected].
  • # Contributed equally.
PMID: 41857368 DOI: 10.1038/s41401-026-01764-2
Abstract

Diabetic peripheral neuropathy (DPN), a severe complication of diabetes, is a key risk factor for diabetic foot (DF) that contributes highly to amputation and mortality. The pathogenesis of DPN remains unclear and complex, with no effective treatments currently available. Monoamine Oxidase (MAO), a flavin adenine dinucleotide (FAD)-dependent enzyme, catalyzes the oxidative deamination of critical biogenic amines. The MAO family comprises two subtypes, MAOA and MAOB, which play distinct roles in pathophysiology. In this study, we identified that MAOB but not MAOA is pathologically upregulated in the sciatic nerve (SN) tissues of DPN patients and in the SN/dorsal root ganglion (DRG) tissues of DPN model mice. Notably, the selective MAOB inhibitor Khellin (Khe) effectively alleviated DPN-like pathology in mice. To explore the mechanistic role of MAOB in DPN, we performed proteomic profiling of DRG tissues from DPN mice and validated the findings using a MAOB-specific knockdown DPN mice model treated with adeno-associated virus (AAV) 8-MAOB-RNAi. Our results demonstrate that Khe targets MAOB to mitigate DPN pathology through HIF-1α/BACE1/Aβ/NLRP3/tau pathway, mediated by Schwann cell/DRG neuron crosstalk. All findings suggest that selective MAOB inhibition represents a promising therapeutic strategy for DPN, with Khe as a potential candidate for clinical translation against this disease.

Keywords

NLRP3 inflammasome; Tau; amyloid β-protein (Aβ); diabetic peripheral neuropathy; monoamine oxidase B, Khellin.

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