Preview

Medical Genetics

Advanced search
Open Access Open Access  Restricted Access Subscription Access

Lysosomal storage diseases and neurodegenerative diseases: the molecular basis of comorbidity.

https://doi.org/10.25557/2073-7998.2025.12.140-142

Abstract

This article presents data on the molecular basis of the comorbidity of Gaucher disease, a rare hereditary disorder, with Parkinson’s disease, a common neurodegenerative condition. It is discussed that this association may be broader and extend to other genes of lysosomal storage diseases. Approaches to the treatment of Parkinson’s disease are discussed, that are uncovered as a result of our own data obtained in recent years.

About the Author

S. N. Pchelina
Petersburg Nuclear Physics Institute Named by B.P. Konstantinov of National Research Center «Kurchatov Institute»; Pavlov First Saint-Petersburg State Medical University
Россия


References

1. Zakharova E.Yu., Baydakova G.V., Mikhailova S.V., et al. Lizosomnyye bolezni nakopleniya [Lysosomal storage diseases]. “GEOTAR-Media”, 2021.424p. ISBN 978-5-9704-6321-5. DOI 10.33029/9704-6321-5-LAD-2021-1-424. (In Russ.)

2. Neudorfer O., Giladi N., Elstein D., et al. Occurrence of Parkinson’s syndrome in type I Gaucher disease. QJM. 1996;89(9):691-694. doi:10.1093/qjmed/89.9.691

3. Sidransky E., Nalls M.A., Aasly J.O., et al. Multicenter analysis of glucocerebrosidase mutations in Parkinson’s disease. N Engl J Med. 2009;361(17):1651-1661. doi:10.1056/NEJMoa0901281

4. Hertz E., Chen Y., Sidransky E. Gaucher disease provides a unique window into Parkinson disease pathogenesis. Nat Rev Neurol. 2024;20(9):526-540. doi:10.1038/s41582-024-00999-z

5. Skrahin A., Horowitz M., Istaiti M., et al. GBA1-Associated Parkinson’s Disease Is a Distinct Entity. Int J Mol Sci. 2024;25(13):7102. Published 2024 Jun 28. doi:10.3390/ijms25137102

6. Gan-Or Z., Ozelius L.J., Bar-Shira A., et al. The p.L302P mutation in the lysosomal enzyme gene SMPD1 is a risk factor for Parkinson disease. Neurology. 2013;80(17):1606-1610. doi:10.1212/WNL.0b013e31828f180e

7. Alcalay R.N., Mallett V., Vanderperre B., et al. SMPD1 mutations, activity, and α-synuclein accumulation in Parkinson’s disease. Mov Disord. 2019;34(4):526-535. doi:10.1002/mds.27642

8. Robak L.A., Jansen I.E., van Rooij J., et al. Excessive burden of lysosomal storage disorder gene variants in Parkinson’s disease. Brain. 2017;140(12):3191-3203. doi:10.1093/brain/awx285

9. Zhao Y.W., Pan H.X., Liu Z., et al. The Association Between Lysosomal Storage Disorder Genes and Parkinson’s Disease: A Large Cohort Study in Chinese Mainland Population. Front Aging Neurosci. 2021;13:749109. doi:10.3389/fnagi.2021.749109

10. Straniero L., Rimoldi V., Monfrini E, et al. Role of Lysosomal Gene Variants in Modulating GBA-Associated Parkinson’s Disease Risk. Movement Disorders : Official Journal of the Movement Disorder Society. 2022;37(6):1202-1210. DOI: 10.1002/mds.28987. PMID: 35262230

11. Emelyanov A.K., Usenko T.S., Tesson C., et al. Mutation analysis of Parkinson’s disease genes in a Russian data set. Neurobiol Aging. 2018;71:267.e7-267.e10. doi:10.1016/j.neurobiolaging.2018.06.027

12. Senkevich K., Beletskaia M., Dworkind A., et al. Association of Rare Variants in ARSA with Parkinson’s Disease. Mov Disord. 2023;38(10):1806-1812. doi: 10.1002/mds.29521.

13. Mohamed F.E., Al-Jasmi F.. Exploring the efficacy and safety of Ambroxol in Gaucher disease: an overview of clinical studies. Front Pharmacol. 2024;15:1335058. doi:10.3389/fphar.2024.1335058

14. den Heijer J.M., Kruithof A.C., Moerland M., et al. A Phase 1B Trial in GBA1-Associated Parkinson’s Disease of BIA-28-6156, a Glucocerebrosidase Activator. Mov Disord. 2023;38(7):1197-1208. doi:10.1002/mds.29346

15. Kopytova A.E., Rychkov G.N., Nikolaev M.A., et al. Ambroxol increases glucocerebrosidase (GCase) activity and restores GCase translocation in primary patient-derived macrophages in Gaucher disease and Parkinsonism. Parkinsonism Relat Disord. 2021;84:112 121. doi:10.1016/j.parkreldis.2021.02.003

16. Zhu X., Gao .J, Qiu C. Integrative analysis reveals key lysosomal genes as potential therapeutic targets in Alzheimer’s disease. Metab Brain Dis. 2024;39(7):1433-1445. doi:10.1007/s11011-024-01409-5


Review

For citations:


Pchelina S.N. Lysosomal storage diseases and neurodegenerative diseases: the molecular basis of comorbidity. Medical Genetics. 2025;24(12):140-142. (In Russ.) https://doi.org/10.25557/2073-7998.2025.12.140-142

Views: 11

JATS XML

ISSN 2073-7998 (Print)