Increased expression of coronin-1a in amyotrophic lateral sclerosis: a potential diagnostic biomarker and therapeutic target

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.

Keywords

amyotrophic lateral sclerosis / coronin-1a / autophagy / pathogenesis

References

[1] van EsMA, HardimanO, ChioA, Al-ChalabiA, PasterkampRJ, VeldinkJH, van den BergLH. Amyotrophic lateral sclerosis. Lancet 2017; 390( 10107): 2084– 2098

[2] FangT, Al KhleifatA, MeurgeyJH, JonesA, LeighPN, BensimonG, Al-ChalabiA. Stage at which riluzole treatment prolongs survival in patients with amyotrophic lateral sclerosis: a retrospective analysis of data from a dose-ranging study. Lancet Neurol 2018; 17( 5): 416– 422

[3] JaiswalMK. Riluzole and edaravone: a tale of two amyotrophic lateral sclerosis drugs. Med Res Rev 2019; 39( 2): 733– 748

[4] ZhangJ, LiuY, LiuX, LiS, ChengC, ChenS, LeW. Dynamic changes of CX3CL1/CX3CR1 axis during microglial activation and motor neuron loss in the spinal cord of ALS mouse model. Transl Neurodegener 2018; 7( 1): 35

[5] OskarssonB, GendronTF, StaffNP. Amyotrophic lateral sclerosis: an update for 2018. Mayo Clin Proc 2018; 93( 11): 1617– 1628

[6] MejziniR FlynnLL PitoutIL FletcherS WiltonSD AkkariPA. ALS genetics, mechanisms, and therapeutics: where are we now? Front Neurosci 2019; 13: 1310

[7] HardimanO, van den BergLH, KiernanMC. Clinical diagnosis and management of amyotrophic lateral sclerosis. Nat Rev Neurol 2011; 7( 11): 639– 649

[8] LiuX, GaoY, LinX, LiL, HanX, LiuJ. The coronin family and human disease. Curr Protein Pept Sci 2016; 17( 6): 603– 611

[9] FerrariG, LangenH, NaitoM, PietersJ. A coat protein on phagosomes involved in the intracellular survival of mycobacteria. Cell 1999; 97( 4): 435– 447

[10] FordML. Coronin-1, king of alloimmunity. Immunity 2019; 50( 1): 3– 5

[11] LiL, ZhangX, LeW. Altered macroautophagy in the spinal cord of SOD1 mutant mice. Autophagy 2008; 4( 3): 290– 293

[12] BrooksBR, MillerRG, SwashM, MunsatTL; World Federation of Neurology Research Group on Motor Neuron Diseases. El Escorial revisited: revised criteria for the diagnosis of amyotrophic lateral sclerosis. Amyotroph Lateral Scler Other Motor Neuron Disord 2000; 1( 5): 293– 299

[13] Cui L, Pu C, Fan D. Chinese guidelines for diagnosis and treatment of amyotrophic lateral sclerosis. Chin J Neurol (Zhonghua Shen Jing Ke Za Zhi) 2012; 45(7): 531−533 (in Chinese)

[14] KraemerM, BuergerM, BerlitP. Diagnostic problems and delay of diagnosis in amyotrophic lateral sclerosis. Clin Neurol Neurosurg 2010; 112( 2): 103– 105

[15] XuX Shen D GaoY ZhouQ NiY Meng H ShiH LeW Chen S ChenS. A perspective on therapies for amyotrophic lateral sclerosis: can disease progression be curbed? Transl Neurodegener 2021; 10( 1): 29

[16] HenselN ClausP. The actin cytoskeleton in SMA and ALS: how does it contribute to motoneuron degeneration? Neuroscientist 2018; 24( 1): 54− 72

[17] OberstadtM, ClaßenJ, ArendtT, HolzerM. TDP-43 and cytoskeletal proteins in ALS. Mol Neurobiol 2018; 55( 4): 3143– 3151

[18] ZhangX, ChenS, SongL, TangY, ShenY, JiaL, LeW. MTOR-independent, autophagic enhancer trehalose prolongs motor neuron survival and ameliorates the autophagic flux defect in a mouse model of amyotrophic lateral sclerosis. Autophagy 2014; 10( 4): 588– 602

[19] ZhouQM, ZhangJJ, LiS, ChenS, LeWD. n-butylidenephthalide treatment prolongs life span and attenuates motor neuron loss in SOD1^G93A mouse model of amyotrophic lateral sclerosis. CNS Neurosci Ther 2017; 23( 5): 375– 385

[20] ZhangJJ, ZhouQM, ChenS, LeWD. Repurposing carbamazepine for the treatment of amyotrophic lateral sclerosis in SOD1-G93A mouse model. CNS Neurosci Ther 2018; 24( 12): 1163– 1174

[21] MartorellaM, BarfordK, WinklerB, DeppmannCD. Emergent role of coronin-1a in neuronal signaling. Vitam Horm 2017; 104 : 113– 131

[22] SuoD, ParkJ, HarringtonAW, ZweifelLS, MihalasS, DeppmannCD. Coronin-1 is a neurotrophin endosomal effector that is required for developmental competition for survival. Nat Neurosci 2014; 17( 1): 36– 45

[23] BoseDasguptaS, PietersJ. Coronin 1 trimerization is essential to protect pathogenic mycobacteria within macrophages from lysosomal delivery. FEBS Lett 2014; 588( 21): 3898– 3905

[24] SetoS, TsujimuraK, KoideY. Coronin-1a inhibits autophagosome formation around Mycobacterium tuberculosis-containing phagosomes and assists mycobacterial survival in macrophages. Cell Microbiol 2012; 14( 5): 710– 727

[25] JayachandranR, PietersJ. Regulation of immune cell homeostasis and function by coronin 1. Int Immunopharmacol 2015; 28( 2): 825– 828

[26] JayachandranR, SundaramurthyV, CombaluzierB, MuellerP, KorfH, HuygenK, MiyazakiT, AlbrechtI, MassnerJ, PietersJ. Survival of mycobacteria in macrophages is mediated by coronin 1-dependent activation of calcineurin. Cell 2007; 130( 1): 37– 50

[27] TongY, SongF. Intracellular calcium signaling regulates autophagy via calcineurin-mediated TFEB dephosphorylation. Autophagy 2015; 11( 7): 1192– 1195

[28] HuYX Han XS JingQ. Ca(2+) ion and autophagy. In: Qin ZH. Autophagy: Biology and Diseases. Advances in Experimental Medicine and Biology, vol 1206. Singapore: Springer, 2019: 151− 166

Acknowledgements

This work was supported by the Clinical Research Plan of SHDC (No. SHDC2020CR2027B), Shanghai Young Top-notch Talent Support Program, Double Hundred Talents Support Program of Shanghai Jiao Tong University School of Medicine, and the projects sponsored by the development fund for Shanghai talents. The funders had no role in the design and conduction of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Compliance with ethics guidelines

Qinming Zhou, Lu He, Jin Hu, Yining Gao, Dingding Shen, You Ni, Yuening Qin, Huafeng Liang, Jun Liu, Weidong Le, and Sheng Chen declare that they have no conflict of interest. This study was approved by the Ethics Committee of Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. We committed to protecting the patients’ privacy and complying with the Helsinki Declaration.

Electronic Supplementary Material

Supplementary material is available in the online version of this article at https://doi.org/10.1007/s11684-021-0905-y and is accessible for authorized users.

RIGHTS & PERMISSIONS

2022 Higher Education Press