ATP13A2 protects dopaminergic neurons in Parkinson's disease: from biology to pathology

Tao Dang; Wen-Jing Cao; Rong Zhao; Ming Lu; Gang Hu; Chen Qiao

doi:10.7555/JBR.36.20220001

Volume 36 Issue 2

Mar. 2022

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The Journal of Biomedical Research > 2022 > 36(2): 98-108. > DOI: 10.7555/JBR.36.20220001

Tao Dang, Wen-Jing Cao, Rong Zhao, Ming Lu, Gang Hu, Chen Qiao. ATP13A2 protects dopaminergic neurons in Parkinson's disease: from biology to pathology[J]. The Journal of Biomedical Research, 2022, 36(2): 98-108. DOI: 10.7555/JBR.36.20220001

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ATP13A2 protects dopaminergic neurons in Parkinson's disease: from biology to pathology

Tao Dang^{1, 2},
Wen-Jing Cao⁴,
Rong Zhao¹,
Ming Lu³,
Gang Hu³,
Chen Qiao^{1, 2, ,}

1.
Department of Clinical Pharmacy, the Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212001, China
2.
College of Pharmacy, Jiangsu University, Zhenjiang, Jiangsu 212013, China
3.
Jiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology, Nanjing Medical University, Nanjing, Jiangsu 211166, China
4.
Department of Clinical Pharmacy, Xiangtan Central Hospital, Xiangtan, Hunan 411100, China

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Corresponding author:
Chen Qiao, Department of ClinicalPharmacy, the Affiliated Hospital of Jiangsu University, 438 Jiefang Road, Zhenjiang, Jiangsu 212001, China. Tel: +86-511-86867879, E-mail: qiaochennjmu@126.com
Received Date: December 31, 2021
Revised Date: February 25, 2022
Accepted Date: March 01, 2022
Available Online: March 27, 2022

Graphical Abstract

Abstract

Abstract

As a late endosomal/lysosomal transport protein of the P5-type, ATP13A2 is capable of removing the abnormal accumulation of α-synuclein, which maintains the homeostasis of metal ions and polyamines in the central nervous system. Furthermore, ATP13A2 regulates the normal function of several organelles such as lysosomes, endoplasmic reticulum (ER) and mitochondria, and maintains the normal physiological activity of neural cells. Especially, ATP13A2 protects dopaminergic (DA) neurons against environmental or genetically induced Parkinson's disease (PD). As we all know, PD is a neurodegenerative disease characterized by the loss of DA neurons in the substantia nigra pars compacta. An increasing number of studies have reported that the loss-of-function of ATP13A2 affects normal physiological processes of various organelles, leading to abnormalities and the death of DA neurons. Previous studies in our laboratory have also shown that ATP13A2 deletion intensifies the neuroinflammatory response induced by astrocytes, thus inducing DA neuronal injury. In addition to elucidating the normal structure and function of ATP13A2, this review summarized the pathological mechanisms of ATP13A2 mutations leading to PD in existing literature studies, deepening the understanding of ATP13A2 in the pathological process of PD and other related neurodegenerative diseases. This review provides inspiration for investigators to explore the essential regulatory role of ATP13A2 in PD in the future.
- ATP13A2,
- Parkinson's disease,
- dopaminergic neurons,
- lysosome,
- α-synuclein

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References (74)

References

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