Activation of α7nAChR reduces inflammation and apoptosis, promoting muscle regeneration through the AKT-FOXO1 pathway PMID: 41933047

ADC Targets in Oncology

2026-04-10

Activation of α7nAChR reduces inflammation and apoptosis, promoting muscle regeneration through the AKT-FOXO1 pathway

Cell Death Differ. 2026 Apr 3. doi: 10.1038/s41418-026-01738-1.

Xiaolu Jin ^# ¹ ² ³ , Ya Zhou ^# ¹ , Luning Sun ^# ⁴ , Li Li ¹ ⁵ , Chaozhu Zheng ¹ , Zhongliang Shan ¹ , Chao Ding ⁵ , Dongdong Huang ⁶ , Qipeng Zhang ⁷ , Rongrong Fan ⁸ , Guan Sun ⁹ , Meihong Shen ¹⁰ ¹¹ , Hongwei Wang ¹² ¹³ , Zhiqiang Huang ¹⁴ ¹⁵

Affiliations

1. Rehabilitation department, Affiliated Yancheng No.1 People's Hospital, State Key Laboratory of Pharmaceutical Biotechnology, State Key Laboratory of Analytical Chemistry for Life Science, Medical School, Nanjing University, Yancheng, China.
2. College of Acupuncture Moxibustion and Tuina, Nanjing University of Chinese Medicine, Nanjing, China.
3. Key Laboratory of Acupuncture and Medicine Research of Ministry of Education, Nanjing University of Chinese Medicine, Nanjing, China.
4. Department of Sports Medicine, Shanghai General Hospital, Shanghai Jiaotong University, Shanghai, China.
5. Affiliated Nanjing Drum Tower Hospital, Medical School, Nanjing University, Nanjing, China.
6. Department of Gastrointestinal Surgery, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, China.
7. School of Life Sciences, 163 Xianlin Avenue, Nanjing University, Nanjing, China.
8. Department of Medicine Huddinge, Unit for Gastroenterology and Nutrition, Karolinska Institute, Huddinge, Sweden.
9. Neurosurgery department, Affiliated Yancheng No.1 People's Hospital, Medical School, Nanjing University, Yancheng, China. [email protected].
10. College of Acupuncture Moxibustion and Tuina, Nanjing University of Chinese Medicine, Nanjing, China. [email protected].
11. Key Laboratory of Acupuncture and Medicine Research of Ministry of Education, Nanjing University of Chinese Medicine, Nanjing, China. [email protected].
12. Rehabilitation department, Affiliated Yancheng No.1 People's Hospital, State Key Laboratory of Pharmaceutical Biotechnology, State Key Laboratory of Analytical Chemistry for Life Science, Medical School, Nanjing University, Yancheng, China. [email protected].
13. Affiliated Nanjing Drum Tower Hospital, Medical School, Nanjing University, Nanjing, China. [email protected].
14. Rehabilitation department, Affiliated Yancheng No.1 People's Hospital, State Key Laboratory of Pharmaceutical Biotechnology, State Key Laboratory of Analytical Chemistry for Life Science, Medical School, Nanjing University, Yancheng, China. [email protected].
15. Affiliated Nanjing Drum Tower Hospital, Medical School, Nanjing University, Nanjing, China. [email protected].
# Contributed equally.

Abstract

Denervation induces severe muscle atrophy characterized by inflammatory responses and tissue degradation, with limited effective therapeutic options. This study investigates the role of the α7 nicotinic acetylcholine receptor (α7nAChR) in denervation-induced muscle atrophy and evaluates electroacupuncture (EA) as a potential treatment strategy. Using a sciatic nerve transection mouse model, we observe that denervation decreases α7nAChR expression, activates proteolytic pathways. We find that α7nAChR degradation is associated with the activation of inflammatory cytokines and the Caspase pathway. In α7nAChR knockout mice, we demonstrate that α7nAChR modulates Mitochondrial Metabolism and fiber-type composition. It exerts protective effects by activating the AKT-FOXO1 pathway, thereby reducing inflammation and Apoptosis, processes that are critical for muscle regeneration. Additionally, treatment with PNU120596 or EA restores α7nAChR function and alleviates muscle atrophy. Our findings suggest that targeting α7nAChR offers a promising therapeutic approach for muscle wasting following denervation, with potential implications for clinical management and future intervention strategies.