Background: Parkinson’s disease (PD) is a complex, multifactorial neurodegenerative disorder with a pathophysiology deriving from the synergy of abnormal aggregation of neuroinflammation, synuclein and dysfunction of lysosomes, mitochondria and synaptic transport difficulties influenced by genetic and idiopathic factors. Worldwide, PD has a prevalence of 2-3% in people over the age of 65. To date, there is no certified, effective treatment for PD. Aim: The aims of this research were: (i) to present, on the basis of recent advances in molecular genetics and epigenetics, the genomic aspects and challenges of gene therapy trials for PD; (ii) to outline the ethical principles applicable to therapeutic trials for PD. Method: A systematic literature review was carried out to identify relevant articles reporting on genomic aspects and gene therapy in PD from 2001 to October 2023. The search was conducted in French and/or English in three databases: PubMed, Google Scholar and Science Direct. PRISMA guidelines were used in this systematic review. Results: A total of thirty-three publications were selected. An inductive thematic analysis revealed that numerous genetic mutations (SNCA, Parkin, PINK1, DJ-1, LRRK2, ATP13A2, VPS35, Parkin/PRKN, PINK1, DJ1/PARK7) and epigenetic events such as the action of certain miRNAs (miR-7, miR-153, miR-133b, miR-124, miR-137) are responsible for the onset of PD, and that genetic therapy for this pathology raises ethical questions that need to be elucidated in the light of the bioethical principles of autonomy, beneficence, non-maleficence and justice. Conclusion: There is no zero risk in biotechnology. Then, it will be necessary to assess all the potential risks of Parkinson disease’s gene therapy to make the right decision. It is therefore essential to pursue research and, with the guidance of ethics, to advance treatment options and meet the challenges of brain manipulation and its impact on human identity. The golden rule of medicine remains: “Primum non nocere”.
References
[1]
Oliveira, A.M., Coelho, L., Carvalho, E., Ferreira-Pinto, M.J., Vaz, R. and Aguiar, P. (2023) Machine Learning for Adaptive Deep Brain Stimulation in Parkinson’s Disease: Closing the Loop. Journal of Neurology, 270, 5313-5326. https://doi.org/10.1007/s00415-023-11873-1
[2]
Yadav, H.P. and Li, Y. (2015) The Development of Treatment for Parkinson’s Disease. Advances in Parkinson’s Disease, 4, 59-78.
[3]
Ciurea, A.V., Mohan, A.G., Covache-Busuioc, R.A., Costin, H.P., Glavan, L.A., Corlatescu, A.D., et al. (2023) Unraveling Molecular and Genetic Insights into Neurodegenerative Diseases: Advances in Understanding Alzheimer’s, Parkinson’s, and Huntington’s Diseases and Amyotrophic Lateral Sclerosis. International Journal of Molecular Sciences, 24, Article 10809. https://doi.org/10.3390/ijms241310809
[4]
Rike, W.A. and Stern, S. (2023) Proteins and Transcriptional Dysregulation of the Brain Extracellular Matrix in Parkinson’s Disease: A Systematic Review. International Journal of Molecular Sciences, 24, Article 7435. https://doi.org/10.3390/ijms24087435
[5]
Aghazadeh, N., Beilankouhi, E.A.V., Fakhri, F., Gargari, M.K., Bahari, P., Moghadami, A., et al. (2022) Involvement of Heat Shock Proteins and Parkin/α-Synuclein Axis in Parkinson’s Disease. Molecular Biology Reports, 49, 11061-11070. https://doi.org/10.1007/s11033-022-07900-5
[6]
De Plano, L.M., Calabrese, G., Conoci, S., Guglielmino, S.P.P., Oddo, S. and Caccamo, A. (2022) Applications of CRISPR-Cas9 in Alzheimer’s Disease and Related Disorders. International Journal of Molecular Sciences, 23, Article 8714. https://doi.org/10.3390/ijms23158714
[7]
Over, L., Brüggemann, N. and Lohmann, K. (2021) Therapies for Genetic Forms of Parkinson’s Disease: Systematic Literature Review. Journal of Neuromuscular Diseases, 8, 341-356. https://doi.org/10.3233/JND-200598
[8]
Zohoncon, T.M., Zoure, A.A., Ouedraogo, M.N.L., Ouedraogo, P., Djigma, F.W., Nadembèga, W.M.C., Kabore, R., Ouermi, D., Obiri-Yeboah, D. and Simpore, J. (2023) Presymptomatic Diagnosis and Gene Therapy for Alzheimer’s Disease: Genomic, Therapeutic, and Ethical Aspects: A Systematic Review. Advances in Alzheimer’s Disease, 12, 4.
[9]
Palmieri, I., Poloni, T.E., Medici, V., Zucca, S., Davin, A., Pansarasa, O., et al. (2022) Differential Neuropathology, Genetics, and Transcriptomics in Two Kindred Cases with Alzheimer’s Disease and Lewy Body Dementia. Biomedicines, 10, Article 1687. https://doi.org/10.3390/biomedicines10071687
[10]
Soto, M., Iranzo, A., Lahoz, S., Fernández, M., Serradell, M., Gaig, C., et al. (2022) Serum MicroRNAs Predict Isolated Rapid Eye Movement Sleep Behavior Disorder and Lewy Body Diseases. Movement Disorders: Official Journal of the Movement Disorder Society, 37, 2086-2098. https://doi.org/10.1002/mds.29171
[11]
Ayyildiz, D., Bergonzoni, G., Monziani, A., Tripathi, T., Döring, J., Kerschbamer, E., et al. (2023) CAG Repeat Expansion in the Huntington’s Disease Gene Shapes Linear and Circular RNAs Biogenesis. PLOS Genetics, 19, e1010988. https://doi.org/10.1371/journal.pgen.1010988
[12]
Nassar, A., Satarker, S., Gurram, P.C., Upadhya, D., Fayaz, S.M. and Nampoothiri, M. (2023) Repressor Element-1 Binding Transcription Factor (REST) as a Possible Epigenetic Regulator of Neurodegeneration and MicroRNA-Based Therapeutic Strategies. Molecular Neurobiology, 60, 5557-5577. https://doi.org/10.1007/s12035-023-03437-1
[13]
Hitti, F.L., Yang, A.I., Gonzalez-Alegre, P. and Baltuch, G.H. (2019) Human Gene Therapy Approaches for the Treatment of Parkinson’s Disease: An Overview of Current and Completed Clinical Trials. Parkinsonism & Related Disorders, 66, 16-24. https://doi.org/10.1016/j.parkreldis.2019.07.018
[14]
Merola, A., Van Laar, A., Lonser, R. and Bankiewicz, K. (2020) Gene Therapy for Parkinson’s Disease: Contemporary Practice and Emerging Concepts. Expert Review of Neurotherapeutics, 20, 577-590. https://doi.org/10.1080/14737175.2020.1763794
[15]
Courtin, T. and Brice, A. (2022) Progresses in Parkinson’s Disease Genetics: What Lessons Have We Learnt? Bulletin de l’Académie Nationale de Médecine, 206, 902-908. https://doi.org/10.1016/j.banm.2022.05.002
Paccosi, E. and Proietti-De-Santis, L. (2023) Parkinson’s Disease: From Genetics and Epigenetics to Treatment, a miRNA-Based Strategy. International Journal of Molecular Sciences, 24, Article 9547. https://doi.org/10.3390/ijms24119547
[18]
West, A.B., Moore, D.J., Biskup, S., Bugayenko, A., Smith, W.W., Ross, C.A., et al. (2005) Parkinson’s Disease-Associated Mutations in Leucine-Rich Repeat Kinase 2 Augment Kinase Activity. Proceedings of the National Academy of Sciences of the United States of America, 102, 16842-16847. https://doi.org/10.1073/pnas.0507360102
[19]
Goldberg, M.S., Fleming, S.M., Palacino, J.J., Cepeda, C., Lam, H.A., Bhatnagar, A., et al. (2003) Parkin-Deficient Mice Exhibit Nigrostriatal Deficits But Not Loss of Dopaminergic Neurons. The Journal of Biological Chemistry, 278, 43628-43635. https://doi.org/10.1074/jbc.M308947200
[20]
Rauschendorf, M.A., Jost, M., Stock, F., Zimmer, A., Rösler, B., Rijntjes, M., et al. (2017) Novel Compound Heterozygous Synaptojanin-1 Mutation Causes l-Dopa-Responsive Dystonia-Parkinsonism Syndrome. Movement Disorders: Official Journal of the Movement Disorder Society, 32, 478-480. https://doi.org/10.1002/mds.26876
[21]
Dolgacheva, L.P., Berezhnov, A.V., Fedotova, E.I., Zinchenko, V.P. and Abramov, A.Y. (2019) Role of DJ-1 in the Mechanism of Pathogenesis of Parkinson’s Disease. Journal of Bioenergetics and Biomembranes, 51, 175-188. https://doi.org/10.1007/s10863-019-09798-4
[22]
Li, J., Yu, J., Guo, J., Liu, J., Wan, G., Wei, X., et al. (2023) Nardostachys Jatamansi and Levodopa Combination Alleviates Parkinson’s Disease Symptoms in Rats through Activation of Nrf2 and Inhibition of NLRP3 Signaling Pathways. Pharmaceutical Biology, 61, 1175-1185. https://doi.org/10.1080/13880209.2023.2244176
[23]
Yoon, H.H., Ye, S., Lim, S., Jo, A., Lee, H., Hong, F., et al. (2022) CRISPR-Cas9 Gene Editing Protects from the A53T-SNCA Overexpression-Induced Pathology of Parkinson’s Disease in vivo. The CRISPR Journal, 5, 95-108. https://doi.org/10.1089/crispr.2021.0025
[24]
Chen, V., Moncalvo, M., Tringali, D., Tagliafierro, L., Shriskanda, A., Ilich, E., et al. (2020) The Mechanistic Role of α-Synuclein in the Nucleus: Impaired Nuclear Function Caused by Familial Parkinson’s Disease SNCA Mutations. Human Molecular Genetics, 29, 3107-3121. https://doi.org/10.1093/hmg/ddaa183
[25]
Zhou, X., Xin, J., Fan, N., Zou, Q., Huang, J., Ouyang, Z., et al. (2015) Generation of CRISPR/Cas9-Mediated Gene-Targeted Pigs via Somatic Cell Nuclear Transfer. Cellular and Molecular Life Sciences, 72, 1175-1184. https://doi.org/10.1007/s00018-014-1744-7
[26]
Ahfeldt, T., Ordureau, A., Bell, C., Sarrafha, L., Sun, C., Piccinotti, S., et al. (2020) Pathogenic Pathways in Early-Onset Autosomal Recessive Parkinson’s Disease Discovered Using Isogenic Human Dopaminergic Neurons. Stem Cell Reports, 14, 75-90. https://doi.org/10.1016/j.stemcr.2019.12.005
[27]
Nouri Nojadeh, J., Bildiren Eryilmaz, N.S. and Ergüder, B.I. (2023) CRISPR/Cas9 Genome Editing for Neurodegenerative Diseases. EXCLI Journal, 22, 567-582.
[28]
Mullin, S., Hughes, D., Mehta, A. and Schapira, A.H.V. (2019) Neurological Effects of Glucocerebrosidase Gene Mutations. European Journal of Neurology, 26, 388-e29. https://doi.org/10.1111/ene.13837
[29]
Hanss, Z., Boussaad, I., Jarazo, J., Schwamborn, J.C. and Krüger, R. (2019) Quality Control Strategy for CRISPR-Cas9-Based Gene Editing Complicated by a Pseudogene. Frontiers in Genetics, 10, Article 1297. https://doi.org/10.3389/fgene.2019.01297
[30]
Kanagaraj, N., Beiping, H., Dheen, S.T. and Tay, S.S. (2014) Downregulation of miR-124 in MPTP-Treated Mouse Model of Parkinson’s Disease and MPP Iodide-Treated MN9D Cells Modulates the Expression of the Calpain/cdk5 Pathway Proteins. Neuroscience, 272, 167-179. https://doi.org/10.1016/j.neuroscience.2014.04.039
[31]
Titze-de-Almeida, S.S., Soto-Sánchez, C., Fernandez, E., Koprich, J.B., Brotchie, J.M. and Titze-de-Almeida, R. (2020) The Promise and Challenges of Developing miRNA-Based Therapeutics for Parkinson’s Disease. Cells, 9, Article 841. https://doi.org/10.3390/cells9040841
[32]
Wollert, T. and Hurley, J.H. (2010) Molecular Mechanism of Multivesicular Body Biogenesis by ESCRT Complexes. Nature, 464, 864-869. https://doi.org/10.1038/nature08849
[33]
Zhuang, X., Xiang, X., Grizzle, W., Sun, D., Zhang, S., Axtell, R.C., et al. (2011) Treatment of Brain Inflammatory Diseases by Delivering Exosome Encapsulated Anti-Inflammatory Drugs from the Nasal Region to the Brain. Molecular Therapy: The Journal of the American Society of Gene Therapy, 19, 1769-1779. https://doi.org/10.1038/mt.2011.164
[34]
Mittelbrunn, M. and Sánchez-Madrid, F. (2012) Intercellular Communication: Diverse Structures for Exchange of Genetic Information. Nature Reviews Molecular Cell Biology, 13, 328-335. https://doi.org/10.1038/nrm3335
[35]
Janowski, M., Wagner, D.C. and Boltze, J. (2015) Stem Cell-Based Tissue Replacement after Stroke: Factual Necessity or Notorious Fiction? Stroke, 46, 2354-2363. https://doi.org/10.1161/STROKEAHA.114.007803
[36]
Fang, Y., Gao, T., Zhang, B. and Pu, J. (2018) Recent Advances: Decoding Alzheimer’s Disease with Stem Cells. Frontiers in Aging Neuroscience, 10, Article 77. https://doi.org/10.3389/fnagi.2018.00077
[37]
Zhang, H., Wang, Y., Lv, Q., Gao, J., Hu, L. and He, Z. (2018) MicroRNA-21 Overexpression Promotes the Neuroprotective Efficacy of Mesenchymal Stem Cells for Treatment of Intracerebral Hemorrhage. Frontiers in Neurology, 9, Article 931. https://doi.org/10.3389/fneur.2018.00931
[38]
Entwistle, V.C., Carter, S.M., Cribb, A. and McCaffery, K. (2010) Supporting Patient Autonomy: The Importance of Clinician-Patient Relationships. Journal of General Internal Medicine, 25, 741-745. https://doi.org/10.1007/s11606-010-1292-2
[39]
Gillon, R. (2015) Defending the Four Principles Approach as a Good Basis for Good Medical Practice and Therefore for Good Medical Ethics. Journal of Medical Ethics, 41, 111-116. https://doi.org/10.1136/medethics-2014-102282
[40]
Viaña, J.N.M. (2021) Deep Brain Stimulation for Preclinical and Prodromal Alzheimer’s Disease: Integrating Beneficence, Non-Maleficence, and Autonomy Considerations through Responsible Innovation. AJOB Neuroscience, 12, 236-239. https://doi.org/10.1080/21507740.2021.1941406
[41]
Robillard, J.M., Wu, J.M., Feng, T.L. and Tam, M.T. (2019) Prioritizing Benefits: A Content Analysis of the Ethics in Dementia Technology Policies. Journal of Alzheimer’s Disease, 69, 897-904. https://doi.org/10.3233/JAD-180938
[42]
Miyasaki, J.M., Lim, T.T. and Bhidayasiri, R. (2021) Editorial: Inclusion, Equity, Diversity and Social Justice in Movement Disorders Research. Parkinsonism & Related Disorders, 85, 114-116. https://doi.org/10.1016/j.parkreldis.2021.03.022
[43]
Elnageeb, M.E., Elfaki, I., Adam, K.M., Ahmed, E.M., Elkhalifa, E.M., Abuagla, H.A., et al. (2023) In silico Evaluation of the Potential Association of the Pathogenic Mutations of α Synuclein Protein with Induction of Synucleinopathies. Diseases, 11, Article 115. https://doi.org/10.3390/diseases11030115
[44]
Zimprich, A., Biskup, S., Leitner, P., Lichtner, P., Farrer, M., Lincoln, S., et al. (2004) Mutations in LRRK2 Cause Autosomal-Dominant Parkinsonism with Pleomorphic Pathology. Neuron, 44, 601-607. https://doi.org/10.1016/j.neuron.2004.11.005
[45]
Vozdek, R., Wang, B., Li, K.H., Pramstaller, P.P., Hicks, A.A. and Ma, D.K. (2022) Fluorescent Reporter of Caenorhabditis elegans Parkin: Regulators of Its Abundance and Role in Autophagy-Lysosomal Dynamics. Open Research Europe, 2, 23. https://doi.org/10.12688/openreseurope.14235.1
[46]
Zhu, M., Patel, S.H. and Han, S. (2017) DJ-1, a Parkinson’s Disease Related Protein, Aggregates under Denaturing Conditions and Co-Aggregates with α-Synuclein through Hydrophobic Interaction. Biochimica et Biophysica Acta (BBA)—General Subjects, 1861, 1759-1769. https://doi.org/10.1016/j.bbagen.2017.03.013
[47]
Goker-Alpan, O., Schiffmann, R., LaMarca, M.E., Nussbaum, R.L., McInerney-Leo, A. and Sidransky, E. (2004) Parkinsonism among Gaucher Disease Carriers. Journal of Medical Genetics, 41, 937-940. https://doi.org/10.1136/jmg.2004.024455
[48]
Li, Y., Feng, D., Wang, Z., Zhao, Y., Sun, R., Tian, D., et al. (2019) Ischemia-Induced ACSL4 Activation Contributes to Ferroptosis-Mediated Tissue Injury in Intestinal Ischemia/Reperfusion. Cell Death and Differentiation, 26, 2284-2299. https://doi.org/10.1038/s41418-019-0299-4
[49]
Liu, N., Bai, L., Lu, Z., Gu, R., Zhao, D., Yan, F., et al. (2022) TRPV4 Contributes to ER Stress and Inflammation: Implications for Parkinson’s Disease. Journal of Neuroinflammation, 19, Article No. 26. https://doi.org/10.1186/s12974-022-02382-5
[50]
Fol, R., Braudeau, J., Ludewig, S., Abel, T., Weyer, S.W., Roederer, J.P., et al. (2016) Viral Gene Transfer of APPsα Rescues Synaptic Failure in an Alzheimer’s Disease Mouse Model. Acta Neuropathologica, 131, 247-266. https://doi.org/10.1007/s00401-015-1498-9
[51]
Dar, N.J., John, U., Bano, N., Khan, S. and Bhat, S.A. (2023) Oxytosis/Ferroptosis in Neurodegeneration: The Underlying Role of Master Regulator Glutathione Peroxidase 4 (GPX4). Molecular Neurobiology. https://doi.org/10.1007/s12035-023-03646-8
Ferrari, C., Ingannato, A., Matà, S., Ramat, S., Caremani, L., Bagnoli, S., et al. (2023) Parkinson-ALS with a Novel MAPT Variant. Neurological Sciences. https://doi.org/10.1007/s10072-023-07081-4
[54]
Hsieh, C.H., Shaltouki, A., Gonzalez, A.E., Bettencourt da Cruz, A., Burbulla, L.F., St Lawrence, E., et al. (2016) Functional Impairment in Miro Degradation and Mitophagy Is a Shared Feature in Familial and Sporadic Parkinson’s Disease. Cell Stem Cell, 19, 709-724. https://doi.org/10.1016/j.stem.2016.08.002
[55]
Imaizumi, Y., Okada, Y., Akamatsu, W., Koike, M., Kuzumaki, N., Hayakawa, H., et al. (2012) Mitochondrial Dysfunction Associated with Increased Oxidative Stress and α-Synuclein Accumulation in PARK2 iPSC-Derived Neurons and Postmortem Brain Tissue. Molecular Brain, 5, Article No. 35. https://doi.org/10.1186/1756-6606-5-35
[56]
Ishizu, N., Yui, D., Hebisawa, A., Aizawa, H., Cui, W., Fujita, Y., et al. (2016) Impaired Striatal Dopamine Release in Homozygous Vps35 D620N Knock—In Mice. Human Molecular Genetics, 25, 4507-4517. https://doi.org/10.1093/hmg/ddw279
[57]
Zhou, H., Zhang, J., Shi, H., Li, P., Sui, X., Wang, Y., et al. (2022) Downregulation of CDK5 Signaling in the Dorsal Striatum Alters Striatal Microcircuits Implicating the Association of Pathologies with Circadian Behavior in Mice. Molecular Brain, 15, Article No. 53. https://doi.org/10.1186/s13041-022-00939-2
[58]
Zhu, X.X., Zhong, Y.Z., Ge, Y.W., Lu, K.H. and Lu, S.S. (2018) CRISPR/Cas9-Mediated Generation of Guangxi Bama Minipigs Harboring Three Mutations in α-Synuclein Causing Parkinson’s Disease. Scientific Reports, 8, Article No. 12420. https://doi.org/10.1038/s41598-018-30436-3
[59]
Yao, J., Huang, J., Hai, T., Wang, X., Qin, G., Zhang, H., et al. (2014) Efficient Bi-Allelic Gene Knockout and Site-Specific Knock-In Mediated by TALENs in Pigs. Scientific Reports, 4, Article No. 6926. https://doi.org/10.1038/srep06926
Yang, W., Liu, Y., Tu, Z., Xiao, C., Yan, S., Ma, X., et al. (2019) CRISPR/Cas9-Mediated PINK1 Deletion Leads to Neurodegeneration in Rhesus Monkeys. Cell Research, 29, 334-336. https://doi.org/10.1038/s41422-019-0142-y
[62]
Li, H., Wu, S., Ma, X., Li, X., Cheng, T., Chen, Z., et al. (2021) Co-Editing PINK1 and DJ-1 Genes Via Adeno-Associated Virus-Delivered CRISPR/Cas9 System in Adult Monkey Brain Elicits Classical Parkinsonian Phenotype. Neuroscience Bulletin, 37, 1271-1288. https://doi.org/10.1007/s12264-021-00732-6
[63]
McMillan, K.J., Murray, T.K., Bengoa-Vergniory, N., Cordero-Llana, O., Cooper, J., Buckley, A., et al. (2017) Loss of MicroRNA-7 Regulation Leads to α-Synuclein Accumulation and Dopaminergic Neuronal Loss in vivo. Molecular Therapy, 25, 2404-2414. https://doi.org/10.1016/j.ymthe.2017.08.017
[64]
Asadi, M.R., Abed, S., Kouchakali, G., Fattahi, F., Sabaie, H., Moslehian, M.S., et al. (2023) Competing Endogenous RNA (ceRNA) Networks in Parkinson’s Disease: A Systematic Review. Frontiers in Cellular Neuroscience, 17, Article 1044634. https://doi.org/10.3389/fncel.2023.1044634
[65]
Straniero, L., Rimoldi, V., Samarani, M., Goldwurm, S., Di Fonzo, A., Krüger, R., et al. (2017) The GBAP1 Pseudogene Acts as a ceRNA for the Glucocerebrosidase Gene GBA by Sponging miR-22-3p. Scientific Reports, 7, Article No. 12702. https://doi.org/10.1038/s41598-017-12973-5
[66]
Doxakis, E. (2010) Post-Transcriptional Regulation of α-Synuclein Expression by Mir-7 and Mir-153. The Journal of Biological Chemistry, 285, 12726-12734. https://doi.org/10.1074/jbc.M109.086827
[67]
Miñones-Moyano, E., Porta, S., Escaramís, G., Rabionet, R., Iraola, S., Kagerbauer, B., et al. (2011) MicroRNA Profiling of Parkinson’s Disease Brains Identifies Early Downregulation of miR-34b/c Which Modulate Mitochondrial Function. Human Molecular Genetics, 20, 3067-3078. https://doi.org/10.1093/hmg/ddr210
[68]
Kim, J., Inoue, K., Ishii, J., Vanti, W.B., Voronov, S.V., Murchison, E., et al. (2007) A MicroRNA Feedback Circuit in Midbrain Dopamine Neurons. Science, 317, 1220-1224. https://doi.org/10.1126/science.1140481
[69]
Soreq, H. and Wolf, Y. (2011) NeurimmiRs: MicroRNAs in the Neuroimmune Interface. Trends in Molecular Medicine, 17, 548-555. https://doi.org/10.1016/j.molmed.2011.06.009
[70]
Chen, Y., Gao, C., Sun, Q., Pan, H., Huang, P., Ding, J., et al. (2017) MicroRNA-4639 Is a Regulator of DJ-1 Expression and a Potential Early Diagnostic Marker for Parkinson’s Disease. Frontiers in Aging Neuroscience, 9, Article 232. https://doi.org/10.3389/fnagi.2017.00232
[71]
Jiang, Y., Liu, J., Chen, L., Jin, Y., Zhang, G., Lin, Z., et al. (2019) Serum Secreted miR-137-Containing Exosomes Affects Oxidative Stress of Neurons by Regulating OXR1 in Parkinson’s Disease. Brain Research, 1722, Article ID: 146331. https://doi.org/10.1016/j.brainres.2019.146331
