Early downregulation of hsa-miR-144-3p in serum from drug-naïve Parkinson’s disease patients

Periñán, María Teresa; Adarmes‐Gómez, Astrid; Azevedo, Tiago; Bacalini, Maria Giulia; Baldelli, Luca; Bartoletti-Stella, Anna; Bhatia, Kailash P.; Bonilla‐Toribio, Marta; Boninsegna, Claudia; Broli, Marcella; Buiza‐Rueda, Dolores; Calandra‐Buonaura, Giovanna; Capellari, Sabina; Carrión‐Claro, Mario; Cilea, Rosalia; Clayton, Robert J.; Cortelli, Pietro; Molin, Alessandra Dal; Luca, Silvia De; Massis, Patrizia De; Dimitri, Giovanna Maria; Doykov, Ivan; Escuela-Martin, Rocio; Fabbri, Giovanni; Franceschi, Claudio; Gabellini, A. S.; Garagnani, Paolo; Giuliani, Cristina; Gómez‐Garre, Pilar; Guaraldi, Pietro; Hägg, Sara; Hällqvist, Jenny; Halsband, Claire; Heywood, Wendy; Houlden, Henry; Huertas, Ismae; Jesús, Silvia; Jylhävä, Juulia; Labrador‐Espinosa, Miguel A.; Licari, Cristina; Lió, Píetro; Luchinat, Claudio; Macías, Daniel; Macrì, S.; Magrinelli, Francesca; Rodríguez, Jesús Núñez; Delledonne, Massimo; Maturo, Maria Giovanna; Mengozzi, Giacomo; Meoni, Gaia; Mignani, Francesco; Milazzo, Maddalena; Mills, Kevin; Mir, Pablo; Mollenhauer, Brit; Nardini, Christine; Nassetti, Stefania; Pedersen, Nancy L.; Periñán-Tocino, Maria Teresa; Pirazzini, Chiara; Provini, Federica; Ravaioli, Francesco; Sala, Claudia; Sambati, Luisa; Scaglione, Cesa; Schade, Sebastian; Schreglmann, Sebastian; Spasov, S; Strom, Stephen C.; Tejera‐Parrado, Cristina; Tenori, Leonardo; Trenkwalder, Claudia; Turano, Paola; Valzania, Franco; Ortega, Rosario Vigo; Williams, Dylan M; Xumerle, Luciano; Zago, Elisa

doi:10.1038/s41598-022-05227-6

Cited by 16 publications

(14 citation statements)

References 67 publications

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“…A fundamental pathological change of PD is the aberrant buildup of α-syn at the presynaptic terminals in a diseased state (26,27). The release of neurotransmitters is highly associated with soluble attachment proteins.…”

Section: Discussionmentioning

confidence: 99%

The safety and effectiveness of α-synuclein immunotherapy vs. placebo for the treatment of Parkinson’s disease: a systematic review and meta-analysis

Zhang

Wang

et al. 2022

Ann Palliat Med

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Background: There is no consensus on the efficacy of using α-synuclein as the primary immunotherapy site for Parkinson's disease (PD). The present study sought to investigate the safety and effectiveness of α-synuclein immunotherapy for treating PD. Methods:The databases of CNKI, CBM, Cochrane Library, PubMed, Web of Science, and Embase were searched for randomized controlled trials (RCTs). Cochrane Collaboration's bias assessment tool was used to assess the risk of bias in the included articles, and the included PD patients older than 18 years adopted immunotherapy. Stata 15.0 was employed for statistical analysis.Results: A total of 6 RCTs were eligible for the present study, involving 606 immunotherapy recipients (using alpha-synuclein immunotherapy) and 254 control individuals (placebo). Our meta-analysis found no statistical difference in the Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) total score [weighted mean difference (WMD): −0.72, 95% confidence interval (CI): −1.56 to 0.13, P=0.099], adverse event incidence [relative risk (RR): 1.06, 95% CI: 0.98 to 1.15, P=0.150], headache incidence (RR: 0.95, 95% CI: 0.67 to 1.34, P=0.773), and constipation incidence (RR: 1.47, 95% CI: 0.77 to 2.78, P=0.242). However, the infection rate in the immunotherapy group was higher than in the control group (RR: 2.29, 95% CI: 1.40 to 3.74, P=0.003). The above results indicate that immunotherapy is significantly different from placebo in MDS-UPDRS and adverse event incidence, but it can reduce the incidence of infection rate.Conclusions: Existing results showed that α-synuclein immunotherapy had no significant effect on PD. high-quality, multi-center, and large-scale clinical studies are desired to corroborate our findings.

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Section: Discussionmentioning

confidence: 99%

The safety and effectiveness of α-synuclein immunotherapy vs. placebo for the treatment of Parkinson’s disease: a systematic review and meta-analysis

Zhang

Wang

et al. 2022

Ann Palliat Med

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“…It was identified as a negative regulator of host response to RNA viruses in mice models (Rosenberger et al, 2017). Hsa-miR-144 was dysregulated in ALS (Liguori et al, 2018;Raheja et al, 2018), PD (Xing et al, 2020;Zago et al, 2022), AD (Cheng et al, 2013), and MS (Roshani et al, 2021).…”

Section: Other Mirnasmentioning

confidence: 99%

Shared miRNA landscapes of COVID-19 and neurodegeneration confirm neuroinflammation as an important overlapping feature

Trampuž

Vogrinc

Goričar

et al. 2023

Front. Mol. Neurosci.

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IntroductionDevelopment and worsening of most common neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis, have been associated with COVID-19 However, the mechanisms associated with neurological symptoms in COVID-19 patients and neurodegenerative sequelae are not clear. The interplay between gene expression and metabolite production in CNS is driven by miRNAs. These small non-coding molecules are dysregulated in most common neurodegenerative diseases and COVID-19.MethodsWe have performed a thorough literature screening and database mining to search for shared miRNA landscapes of SARS-CoV-2 infection and neurodegeneration. Differentially expressed miRNAs in COVID-19 patients were searched using PubMed, while differentially expressed miRNAs in patients with five most common neurodegenerative diseases (Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, amyotrophic lateral sclerosis, and multiple sclerosis) were searched using the Human microRNA Disease Database. Target genes of the overlapping miRNAs, identified with the miRTarBase, were used for the pathway enrichment analysis performed with Kyoto Encyclopedia of Genes and Genomes and Reactome.ResultsIn total, 98 common miRNAs were found. Additionally, two of them (hsa-miR-34a and hsa-miR-132) were highlighted as promising biomarkers of neurodegeneration, as they are dysregulated in all five most common neurodegenerative diseases and COVID-19. Additionally, hsa-miR-155 was upregulated in four COVID-19 studies and found to be dysregulated in neurodegeneration processes as well. Screening for miRNA targets identified 746 unique genes with strong evidence for interaction. Target enrichment analysis highlighted most significant KEGG and Reactome pathways being involved in signaling, cancer, transcription and infection. However, the more specific identified pathways confirmed neuroinflammation as being the most important shared feature.DiscussionOur pathway based approach has identified overlapping miRNAs in COVID-19 and neurodegenerative diseases that may have a valuable potential for neurodegeneration prediction in COVID-19 patients. Additionally, identified miRNAs can be further explored as potential drug targets or agents to modify signaling in shared pathways.Graphical AbstractShared miRNA molecules among the five investigated neurodegenerative diseases and COVID-19 were identified. The two overlapping miRNAs, hsa-miR-34a and has-miR-132, present potential biomarkers of neurodegenerative sequelae after COVID-19. Furthermore, 98 common miRNAs between all five neurodegenerative diseases together and COVID-19 were identified. A KEGG and Reactome pathway enrichment analyses was performed on the list of shared miRNA target genes and finally top 20 pathways were evaluated for their potential for identification of new drug targets. A common feature of identified overlapping miRNAs and pathways is neuroinflammation. AD, Alzheimer’s disease; ALS, amyotrophic lateral sclerosis; COVID-19, coronavirus disease 2019; HD, Huntington’s disease; KEGG, Kyoto Encyclopedia of Genes and Genomes; MS, multiple sclerosis; PD, Parkinson’s disease.

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“…Dysregulation of miRNA expression profiles has been described in several brain areas and fluids of PD patients, as well as in iPSCs-derived DNs generated from affected patients. Table 2 shows a list of 15 miRNAs (let-7b, miR-34b, miR-124, miR-126, miR-132, miR-133b, miR-144, miR-148b, miR-184, miR-199a, miR-204, miR-218, miR-221, miR-338, miR-425) that were found dysregulated by at least two independent studies in nervous tissues (midbrain, prefrontal cortex, amygdala, laser-micro dissected DNs, or anterior cingulate gyrus) [ 105 , 106 , 107 , 108 , 109 , 110 , 111 , 112 , 113 , 114 , 115 , 116 , 117 , 118 ], iPSC-derived DNs [ 119 ] and circulating fluids (CSF, plasma, serum, peripheral blood) [ 119 , 120 , 121 , 122 , 123 , 124 , 125 , 126 , 127 , 128 , 129 , 130 , 131 , 132 , 133 , 134 , 135 , 136 , 137 , 138 , 139 , 140 , 141 , 142 , 143 , 144 , 145 , 146 , 147 , 148 ] of PD patients, thus supporting their potential utility as biomarkers and/or therapeutic targets.…”

Section: Pdmentioning

confidence: 99%

“…The following PD-specific miRNAs have been reported as potential diagnostic biomarkers in circulating fluids: miR-126 [ 122 ], miR-144 [ 124 ], miR-184 [ 145 ], miR-204 [ 127 ] and miR-221 [ 120 , 128 , 129 , 130 ]. Among them, miR-144 has been proposed as an early biomarker [ 123 ]. Let-7b [ 144 ] and miR-148b [ 146 ] were proposed as biomarkers for differential diagnosis of PD from multiple system atrophy, while miR-204 [ 126 ] and miR-425 [ 132 ] from PSP.…”

Section: Pdmentioning

confidence: 99%

Dysregulated miRNAs as Biomarkers and Therapeutical Targets in Neurodegenerative Diseases

Gentile

Morello

Cognata

et al. 2022

JPM

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Alzheimer’s disease (AD), Parkinson’s disease (PD), and Amyotrophic Lateral Sclerosis (ALS) are representative neurodegenerative diseases (NDs) characterized by degeneration of selective neurons, as well as the lack of effective biomarkers and therapeutic treatments. In the last decade, microRNAs (miRNAs) have gained considerable interest in diagnostics and therapy of NDs, owing to their aberrant expression and their ability to target multiple molecules and pathways. Here, we provide an overview of dysregulated miRNAs in fluids (blood or cerebrospinal fluid) and nervous tissue of AD, PD, and ALS patients. By emphasizing those that are commonly dysregulated in these NDs, we highlight their potential role as biomarkers or therapeutical targets and describe the use of antisense oligonucleotides as miRNA therapies.

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Early downregulation of hsa-miR-144-3p in serum from drug-naïve Parkinson’s disease patients

Cited by 16 publications

References 67 publications

The safety and effectiveness of α-synuclein immunotherapy vs. placebo for the treatment of Parkinson’s disease: a systematic review and meta-analysis

The safety and effectiveness of α-synuclein immunotherapy vs. placebo for the treatment of Parkinson’s disease: a systematic review and meta-analysis

Shared miRNA landscapes of COVID-19 and neurodegeneration confirm neuroinflammation as an important overlapping feature

Dysregulated miRNAs as Biomarkers and Therapeutical Targets in Neurodegenerative Diseases

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