Exosomes are nano-vesicles secreted by cells, which can carry the transfer of intracellular protein and other substances. Parkinson's disease (PD) is one of the neurodegenerative diseases, characterized by the progressive loss of neurons, and the production of α -synuclein is its pathological marker. Studies have shown that during the onset of Parkinson's disease, exosomes mediate the toxic transmission of α -synuclein, which leads to the aggravation of the disease. At the same time, it can also be used as a potential biomarker for PD prodromal diagnosis and a potential drug carrier to help the early diagnosis and treatment of PD. This article will review the research progress of exosomes in the pathogenesis, diagnosis and treatment of PD, with a view to clinical application.

Xue Wenying, Jia Ni. Research Progress of Exosomes in Parkinson's Disease. Academic Journal of Medicine & Health Sciences (2023) Vol. 4, Issue 12: 110-115. https://doi.org/10.25236/AJMHS.2023.041215.

[1] Qi Shige, Yin Peng, Wang Linhong, et al. Prevalence of Parkinson's Disease: A Community-Based Study in China [J]. Movement disorders: official journal of the Movement Disorder Society, 2021, 36(12):2940-2944.

[2] Johnstone R M, Adam M, Hammond J R, et al. Vesicle formation during reticulocyte maturation. Association of plasma membrane activities with released vesicles (exosomes) [J]. The Journal of biological chemistry, 1987, 262(19):9412-9420. 

[3] Pegtel DM, Gould SJ. Exosomes [J]. Annu Rev Biochem, 2019, 88:487-514.

[4] Williams Roger L, Urbé Sylvie. The emerging shape of the ESCRT machinery [J]. Nature reviews. Molecular cell biology, 2007, 8(5):355-368.

[5] Hill Andrew F. Extracellular Vesicles and Neurodegenerative Diseases [J]. The Journal of neuroscience: the official journal of the Society for Neuroscience, 2019, 39(47):9269-9273.

[6] Emmanouilidou Evangelia, Melachroinou Katerina, Roumeliotis Theodoros, et al. Cell-produced alpha-synuclein is secreted in a calcium-dependent manner by exosomes and impacts neuronal survival [J]. The Journal of neuroscience: the official journal of the Society for Neuroscience, 2010, 30(20):6838-6851.

[7] Dutta Suman, Hornung Simon, Kruayatidee Adira, et al. α-Synuclein in blood exosomes immunoprecipitated using neuronal and oligodendroglial markers distinguishes Parkinson's disease from multiple system atrophy [J]. Acta neuropathologica, 2021, 142(3):1-17. 

[8] Agliardi Cristina, Meloni Mario, Guerini Franca Rosa, et al. Oligomeric α-Syn and SNARE complex proteins in peripheral extracellular vesicles of neural origin are biomarkers for Parkinson's disease [J]. Neurobiology of disease, 2020, 148:105185-105185. 

[9] Takuma Ohmichi, Masato Mitsuhashi, Harutsugu Tatebe, et al. Quantification of brain-derived extracellular vesicles in plasma as a biomarker to diagnose Parkinson's and related diseases [J]. Parkinsonism and Related Disorders, 2019, 61:82-87. 

[10] Lässer Cecilia, Seyed Alikhani Vesta, Ekström Karin, et al. Human saliva, plasma and breast milk exosomes contain RNA: uptake by macrophages [J]. Journal of Translational Medicine, 2011, 9(1):9.  

[11] Street Jonathan M, Barran Perdita E, Mackay C Logan, et al. Identification and proteomic profiling of exosomes in human cerebrospinal fluid [J]. Journal of translational medicine, 2012, 10(1):5.

[12] Fraser Kyle B, Moehle Mark S, Alcalay Roy N, et al. Urinary LRRK2 phosphorylation predicts parkinsonian phenotypes in G2019S LRRK2 carriers [J]. Neurology, 2016, 86(11):994-999.

[13] Shi Min, Liu Changqin, Cook Travis J, et al. Plasma exosomal α-synuclein is likely CNS-derived and increased in Parkinson's disease [J]. Acta neuropathologica, 2014, 128(5):639-650. 

[14] Cao Zhentang, Wu Yufeng, Liu Genliang, et al. α-Synuclein in salivary extracellular vesicles as a potential biomarker of Parkinson’s disease [J]. Neuroscience Letters, 2019, 696:114-120. 

[15] Valadi Hadi, Ekström Karin, Bossios Apostolos, et al. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells [J]. Nature cell biology, 2007, 9(6):654-659. 

[16] Xie Shishuai, Niu Wanxiang, Xu Feng, et al. Differential expression and significance of miRNAs in plasma extracellular vesicles of patients with Parkinson's disease [J]. The International journal of neuroscience, 2020, 132(7):11-18.

[17] Yuki Kitamura, Midori Kojima, Toshihito Kurosawa, et al. Proteomic Profiling of Exosomal Proteins for Blood-based Biomarkers in Parkinson's Disease [J]. Neuroscience, 2018, 392:121-128. 

[18] Danzer Karin M, Kranich Lisa R, Ruf Wolfgang P, et al. Exosomal cell-to-cell transmission of alpha synuclein oligomers [J]. Molecular Neurodegeneration, 2012, 7(1):42. 

[19] Arotcarena Marie-Laure, Dovero Sandra, Prigent Alice, et al. Bidirectional gut-to-brain and brain-to-gut propagation of synucleinopathy in non-human primates [J]. Brain : a journal of neurology, 2020, 143(5):1462-1475.

[20] Recasens Ariadna, Dehay Benjamin, Bové Jordi, et al. Lewy body extracts from Parkinson disease brains trigger α-synuclein pathology and neurodegeneration in mice and monkeys [J]. Annals of neurology, 2014, 75(3):351-362. 

[21] Yin Zhenyu, Han Zhaoli, Hu Tianpeng, et al. Neuron-derived exosomes with high miR-21-5p expression promoted polarization of M1 microglia in culture [J]. Brain Behavior and Immunity, 2020, 83:270-282. 

[22] Estes Myka L, McAllister A Kimberley. Alterations in immune cells and mediators in the brain: it's not always neuroinflammation! [J]. Brain pathology (Zurich, Switzerland), 2014, 24(6):623-630.

[23] Bodea Liviu-Gabriel, Wang Yiner, Linnartz-Gerlach Bettina, et al. Neurodegeneration by activation of the microglial complement-phagosome pathway [J]. The Journal of neuroscience: the official journal of the Society for Neuroscience, 2014, 34(25):8546-8556.

[24] Chen Yimeng, Gao Chao, Sun Qian, et al. MicroRNA-4639 Is a Regulator of DJ-1 Expression and a Potential Early Diagnostic Marker for Parkinson’s Disease [J]. Frontiers in Aging Neuroscience, 2017, 9:232.

[25] Kirsty J. McMillan, Tracey K. Murray, Nora Bengoa-Vergniory, et al. Loss of MicroRNA-7 Regulation Leads to α-Synuclein Accumulation and Dopaminergic Neuronal Loss In Vivo [J]. Molecular Therapy, 2017, 25(10):2404-2414.

[26] Miñones-Moyano Elena, Porta Sílvia, Escaramís Georgia, et al. MicroRNA profiling of Parkinson's disease brains identifies early downregulation of miR-34b/c which modulate mitochondrial function [J]. Human molecular genetics, 2011, 20(15):3067-3078.

[27] Fraser Kyle B, Moehle Mark S, Daher João P L, et al. LRRK2 secretion in exosomes is regulated by 14-3-3 [J]. Human molecular genetics, 2013, 22(24):4988-5000. 

[28] Marques Cláudia R, Marote Ana, Mendes-Pinheiro Bárbara, et al. Cell secretome based approaches in Parkinson's disease regenerative medicine [J]. Expert opinion on biological therapy, 2018, 18(12):1-11.

[29] Chen Hongxu, Liang Fuchao, Gu Ping, et al. Exosomes derived from mesenchymal stem cells repair a Parkinson's disease model by inducing autophagy [J]. Cell death & disease, 2020, 11(4):288. 

[30] Wen Liao, Yu Du, Chenghao Zhang, et al. Exosomes: the next generation of endogenous nanomaterials for advanced drug delivery and therapy [J]. Acta Biomaterialia, 2018, 86:1-14.

[31] Qu Mengke, Lin Qing, Huang Luyi, et al. Dopamine-loaded blood exosomes targeted to brain for better treatment of Parkinson's disease [J]. Journal of Controlled Release, 2018, 287:156-166. 

[32] Izco M, Blesa J, Schleef M, et al. Systemic Exosomal Delivery of shRNA Minicircles Prevents Parkinsonian Pathology [J]. Molecular Therapy, 2019, 27(12):2111-2122.

[33] Yang J, Luo S, Zhang J, et al. Exosome-mediated delivery of antisense oligonucleotides targeting α-synuclein ameliorates the pathology in a mouse model of Parkinson's disease [J]. Neurobiology of Disease, 2021, 148:105218.

[34] Sun Ting, Ding Zhexu, Luo Xin, et al. Blood Exosomes Have Neuroprotective Effects in a Mouse Model of Parkinson's Disease [J]. Oxidative Medicine and Cellular Longevity, 2020:3807476.

[35] Appaix Florence, Nissou Marie-France, van der Sanden Boudewijn, et al. Brain mesenchymal stem cells: The other stem cells of the brain? [J]. World journal of stem cells, 2014, 6(2):134-143. 

[36] Volarevic Vladislav, Gazdic Marina, Simovic Markovic Bojana, et al. Mesenchymal stem cell-derived factors: Immuno-modulatory effects and therapeutic potential [J]. BioFactors (Oxford, England), 2017, 43(5):633-644.

[37] Akvilė Jarmalavičiūtė, Virginijus Tunaitis, Ugnė Pivoraitė, et al. Exosomes from dental pulp stem cells rescue human dopaminergic neurons from 6-hydroxy-dopamine-induced apoptosis [J]. Cytotherapy, 2015, 17(7):932-939.

[38] Teixeira Fábio G, Carvalho Miguel M, Panchalingam Krishna M, et al. Impact of the Secretome of Human Mesenchymal Stem Cells on Brain Structure and Animal Behavior in a Rat Model of Parkinson's Disease [J]. Stem cells translational medicine, 2017, 6(2):634-646. 

[39] Li Songpei, Lin Zhongxiao, Jiang Xueyan, et al. Exosomal cargo-loading and synthetic exosome-mimics as potential therapeutic tools [J]. Acta pharmacologica Sinica, 2018, 39(4):542-551. 

[40] Xu Meng, Feng Tao, Liu Bowen, et al. Engineered exosomes: desirable target-tracking characteristics for cerebrovascular and neurodegenerative disease therapies [J]. Theranostics, 2021, 11(18): 8926-8944.