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Genetic Convergence of Parkinson’s Disease and Lysosomal Storage Disorders

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Abstract

Parkinson’s disease is a common progressive neurodegenerative disorder characterized by predominant degeneration of the dopaminergic neurons in the substantia nigra pars compacta and the presence of intracellular inclusions enriched in α-synuclein, resulting in a variety motor and nonmotor symptoms. Lysosomal storage disorders are a group of disorders including Gaucher disease, Niemann-Pick disease, and neuronal ceroid lipofuscinoses caused by the defective activity of lysosomal and nonlysosomal proteins. In addition to an overlap in some clinical features between lysosomal storage disorders and Parkinson’s disease, the two disorders may be also linked pathogenically. There is growing support for the notion that mutations in genes causing lysosomal storage disorders including the glucocerebrosidase gene, the sphingomyelin phosphodiesterase 1 gene, and the NPC1 gene may increase risk for developing Parkinson’s disease. In this review, we discuss the recent advances in the genetic convergence of Parkinson’s disease and lysosomal storage disorders, shedding new light on the understanding of shared pathogenic pathways.

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Acknowledgments

This study was supported by the National Natural Science Foundation of China (81101339, 81271921), Research Fundation for the Doctoral Program of Higher Education of China (20110162110026), Sheng Hua Scholars Program of Central South University, China (H.D.), Construction Fundation for Key Subjects of the Third Xiangya Hospital, Central South University, China (H.D.), the Fundamental Research Funds for the Central Universities of Central South University (2014zzts360), China, the National Parkinson Foundation, USA (J.J.).

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The authors declare that there are no conflicts of interest.

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Authors and Affiliations

  1. Center for Experimental Medicine, The Third Xiangya Hospital, Central South University, 138 Tongzipo Road, Changsha, Hunan, 410013, China

    Hao Deng & Xiaofei Xiu

  2. Department of Neurology, The Third Xiangya Hospital, Central South University, Changsha, China

    Hao Deng

  3. Department of Neurology, Baylor College of Medicine, Houston, TX, USA

    Joseph Jankovic

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  1. Hao Deng
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  2. Xiaofei Xiu
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Correspondence to Hao Deng.

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Hao Deng and Xiaofei Xiu contributed equally to this work.

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Deng, H., Xiu, X. & Jankovic, J. Genetic Convergence of Parkinson’s Disease and Lysosomal Storage Disorders. Mol Neurobiol 51, 1554–1568 (2015). https://doi.org/10.1007/s12035-014-8832-4

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