Exploring the Association between Cathepsin B and Parkinson’s Disease

Author:

Lu Changhao12ORCID,Cai Xinyi3ORCID,Zhi Shilin4,Wen Xiaofen5,Shen Jiaxin6,Ercoli Tommaso7ORCID,Simula Elena Rita2ORCID,Masala Carla8ORCID,Sechi Leonardo A.29ORCID,Solla Paolo17ORCID

Affiliation:

1. Department of Medical, Surgical and Experimental Sciences, University of Sassari, 07100 Sassari, Italy

2. Department of Biomedical Sciences, University of Sassari, 07100 Sassari, Italy

3. Provincial Key Laboratory of Infectious Diseases and Molecular Immunopathology, Department of Pathology, Shantou University Medical College, Shantou 515041, China

4. Department of Gastrointestinal Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China

5. Department of Medical Oncology, Cancer Hospital of Shantou University Medical College, Shantou 515041, China

6. Department of Hematology, The First Affiliated Hospital of Shantou University Medical College, Shantou 515041, China

7. Department of Neurology, University of Sassari, Viale S. Pietro 10, 07100 Sassari, Italy

8. Department of Biomedical Sciences, University of Cagliari, SP 8 Cittadella Universitaria, 09042 Monserrato, Italy

9. Struttura Complessa di Microbiologia e Virologia, Azienda Ospedaliera Universitaria di Sassari, 07100 Sassari, Italy

Abstract

Objective: The aim of this study is to investigate the association between Cathepsin B and Parkinson’s Disease (PD), with a particular focus on determining the role of N-acetylaspartate as a potential mediator. Methods: We used summary-level data from Genome-Wide Association Studies (GWAS) for a two-sample Mendelian randomization (MR) analysis, exploring the association between Cathepsin B (3301 cases) and PD (4681 cases). A sequential two-step MR approach was applied (8148 cases) to study the role of N-acetylaspartate. Results: The MR analysis yielded that genetically predicted elevated Cathepsin B levels correlated with a reduced risk of developing PD (p = 0.0133, OR: 0.9171, 95% CI: 0.8563–0.9821). On the other hand, the analysis provided insufficient evidence to determine that PD affected Cathepsin B levels (p = 0.8567, OR: 1.0035, 95% CI: 0.9666–1.0418). The estimated effect of N-acetylaspartate in this process was 7.52% (95% CI = −3.65% to 18.69%). Conclusions: This study suggested that elevated Cathepsin B levels decreased the risk of developing PD, with the mediation effect of N-acetylaspartate. Further research is needed to better understand this relationship.

Publisher

MDPI AG

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