Increased expression of coronin-1a in amyotrophic lateral sclerosis: a potential diagnostic biomarker and therapeutic target.
10.1007/s11684-021-0905-y
- Author:
Qinming ZHOU
1
;
Lu HE
1
;
Jin HU
2
;
Yining GAO
1
;
Dingding SHEN
1
;
You NI
1
;
Yuening QIN
3
;
Huafeng LIANG
4
;
Jun LIU
5
;
Weidong LE
6
;
Sheng CHEN
7
Author Information
1. Department of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
2. Department of Neurology, the First Hospital of Jiaxing & the Affiliated Hospital of Jiaxing University, Jiaxing, 314000, China.
3. Department of Dermatology, The People's Hospital of Rushan, Weihai, 264500, China.
4. Department of Neurology, Xinrui Hospital, Wuxi, 214000, China.
5. Department of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China. jly0520@hotmail.com.
6. Institute of Neurology, Sichuan Academy of Medical Sciences-Sichuan Provincial Hospital, Chengdu, 610072, China. wdle@sibs.ac.cn.
7. Department of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China. mztcs@163.com.
- Publication Type:Journal Article
- Keywords:
amyotrophic lateral sclerosis;
autophagy;
coronin-1a;
pathogenesis
- MeSH:
Mice;
Animals;
Amyotrophic Lateral Sclerosis/pathology*;
Calcineurin/metabolism*;
Motor Neurons/pathology*;
Microfilament Proteins/metabolism*;
Cytoskeletal Proteins/metabolism*
- From:
Frontiers of Medicine
2022;16(5):723-735
- CountryChina
- Language:English
-
Abstract:
Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disease. At present, no definite ALS biomarkers are available. In this study, exosomes from the plasma of patients with ALS and healthy controls were extracted, and differentially expressed exosomal proteins were compared. Among them, the expression of exosomal coronin-1a (CORO1A) was 5.3-fold higher than that in the controls. CORO1A increased with disease progression at a certain proportion in the plasma of patients with ALS and in the spinal cord of ALS mice. CORO1A was also overexpressed in NSC-34 motor neuron-like cells, and apoptosis, oxidative stress, and autophagic protein expression were evaluated. CORO1A overexpression resulted in increased apoptosis and oxidative stress, overactivated autophagy, and hindered the formation of autolysosomes. Moreover, CORO1A activated Ca2+-dependent phosphatase calcineurin, thereby blocking the fusion of autophagosomes and lysosomes. The inhibition of calcineurin activation by cyclosporin A reversed the damaged autolysosomes. In conclusion, the role of CORO1A in ALS pathogenesis was discovered, potentially affecting the disease onset and progression by blocking autophagic flux. Therefore, CORO1A might be a potential biomarker and therapeutic target for ALS.
