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  1. Article ; Online: Clinical outcome prediction from analysis of microelectrode recordings using deep learning in subthalamic deep brain stimulation for Parkinson`s disease.

    Park, Kwang Hyon / Sun, Sukkyu / Lim, Yong Hoon / Park, Hye Ran / Lee, Jae Meen / Park, Kawngwoo / Jeon, Beomseok / Park, Hee-Pyoung / Kim, Hee Chan / Paek, Sun Ha

    PloS one

    2021  Volume 16, Issue 1, Page(s) e0244133

    Abstract: ... treatment for improving the motor symptoms of advanced Parkinson's disease (PD). Accurate positioning ...

    Abstract Background: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective treatment for improving the motor symptoms of advanced Parkinson's disease (PD). Accurate positioning of the stimulation electrodes is necessary for better clinical outcomes.
    Objective: We applied deep learning techniques to microelectrode recording (MER) signals to better predict motor function improvement, represented by the UPDRS part III scores, after bilateral STN DBS in patients with advanced PD. If we find the optimal stimulation point with MER by deep learning, we can improve the clinical outcome of STN DBS even under restrictions such as general anesthesia or non-cooperation of the patients.
    Methods: In total, 696 4-second left-side MER segments from 34 patients with advanced PD who underwent bilateral STN DBS surgery under general anesthesia were included. We transformed the original signal into three wavelets of 1-50 Hz, 50-500 Hz, and 500-5,000 Hz. The wavelet-transformed MER was used for input data of the deep learning. The patients were divided into two groups, good response and moderate response groups, according to DBS on to off ratio of UPDRS part III score for the off-medication state, 6 months postoperatively. The ratio were used for output data in deep learning. The Visual Geometry Group (VGG)-16 model with a multitask learning algorithm was used to estimate the bilateral effect of DBS. Different ratios of the loss function in the task-specific layer were applied considering that DBS affects both sides differently.
    Results: When we divided the MER signals according to the frequency, the maximal accuracy was higher in the 50-500 Hz group than in the 1-50 Hz and 500-5,000 Hz groups. In addition, when the multitask learning method was applied, the stability of the model was improved in comparison with single task learning. The maximal accuracy (80.21%) occurred when the right-to-left loss ratio was 5:1 or 6:1. The area under the curve (AUC) was 0.88 in the receiver operating characteristic (ROC) curve.
    Conclusion: Clinical improvements in PD patients who underwent bilateral STN DBS could be predicted based on a multitask deep learning-based MER analysis.
    MeSH term(s) Aged ; Anesthesia, General ; Area Under Curve ; Deep Brain Stimulation ; Deep Learning ; Female ; Humans ; Male ; Microelectrodes ; Middle Aged ; Parkinson Disease/pathology ; Parkinson Disease/therapy ; ROC Curve ; Severity of Illness Index ; Subthalamic Nucleus/physiopathology ; Treatment Outcome ; Wavelet Analysis
    Language English
    Publishing date 2021-01-26
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2267670-3
    ISSN 1932-6203 ; 1932-6203
    ISSN (online) 1932-6203
    ISSN 1932-6203
    DOI 10.1371/journal.pone.0244133
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Artist’s creative contributions in the context of interdisciplinary research

    Kyong-Mi Paek

    Creativity Studies, Vol 12, Iss

    2019  Volume 1

    Abstract: While expectations regarding art’s potential contributions to the interdisciplinary research ... of the social context in which the efforts of individuals emerge and are assessed, the study examines Ko’s ... as a leading artist of Yatoo, a bioregionally conscious artist community. Ko’s responses to the opportunities ...

    Abstract While expectations regarding art’s potential contributions to the interdisciplinary research context continue to grow, the creative endeavors of individual artists remain under-examined, perhaps because of the inter-relational nature of joint research settings. To explore, how artists navigate their contribution to a given research community, this study reviews the art practice of Seung-Hyun Ko, who participated in Science Walden, a Convergent Research Center carrying out an interdis-ciplinary research project that aimed to build an ecologically sustainable community. Drawing on comprehensive views of creativity that emphasize the importance of the social context in which the efforts of individuals emerge and are assessed, the study examines Ko’s recent collaborative practice in Science Walden within the larger context of his long-term practice as a leading artist of Yatoo, a bioregionally conscious artist community. Ko’s responses to the opportunities and challenges of his involvement in these two interrelated contexts disclose the value of the creative dynamics of interdisciplinary research, with implications for the increasingly diverse interdisciplinary research practices emerging within science and technology. Santrauka Nors lūkesčiai dėl galimo meno indėlio į tarpdalykinių mokslinių tyrimų kontekstą ir toliau auga, paskirų menininkų kūrybinės pastangos lieka nepakankamai išnagrinėtos galbūt dėl nustatytų bendrojo moksliniams tyrimams taikomo tarpusavio santykių pobūdžio. Siekiant ištirti, kaip mokslininkai integruoja savo indėlį į konkrečią mokslinius tyrimus atliekančią bendruomenę, šiame straipsnyje apžvelgiama meno praktika, plėtojama Seung-Hyuno Ko, dirbusio Konvergencinių mokslinių tyrimų centre Science Walden, kuriame vykdomas tarpdalykinis mokslinių tyrimų projektas, o šio tikslas – sukurti ekologiniu požiūriu tvarią bendruomenę. Remiantis išsamiais požiūriais į kūrybiškumą, pabrėžiančiais socialinio konteksto, kuriame randasi individualios pastangos ir kuriame jos yra įvertinamos, svarbą, ...
    Keywords collaboration ; comprehensive views ; creative practice ; interdisciplinary research ; Science Walden ; Yatoo ; Social sciences (General) ; H1-99
    Subject code 700
    Language English
    Publishing date 2019-05-01T00:00:00Z
    Publisher Vilnius Gediminas Technical University
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: CaLecRK-S.5, a pepper L-type lectin receptor kinase gene, accelerates Phytophthora elicitin-mediated defense response.

    Woo, Joo Yong / Kim, Young Jin / Paek, Kyung-Hee

    Biochemical and biophysical research communications

    2020  Volume 524, Issue 4, Page(s) 951–956

    Abstract: ... PAMPs) by pattern-recognition receptors (PRRs) located on the plant cell surface. CaLecRK-S.5, a pepper ... activation. To further elucidate the molecular mechanism of CaLecRK-S.5, transgenic tobacco plants were ... of CaLecRK-S.5, but this accumulation was completely abolished in homozygous transgenic plants ...

    Abstract Innate immunity in plants relies on the recognition of pathogen-associated molecular patterns (PAMPs) by pattern-recognition receptors (PRRs) located on the plant cell surface. CaLecRK-S.5, a pepper L-type lectin receptor kinase, has been shown to confer broad-spectrum resistance through priming activation. To further elucidate the molecular mechanism of CaLecRK-S.5, transgenic tobacco plants were generated in this study. Interestingly, hemizygous transgenic plants exhibited a high accumulation of CaLecRK-S.5, but this accumulation was completely abolished in homozygous transgenic plants by a cosuppression mechanism. Gain-of-function and loss-of-function analyses revealed that CaLecRK-S.5 plays a positive role in Phytophthora elicitin-mediated defense responses.
    MeSH term(s) Phytophthora infestans/immunology ; Piper/genetics ; Piper/immunology ; Plant Diseases/genetics ; Plant Diseases/immunology ; Plant Diseases/parasitology ; Plant Immunity ; Plant Proteins/genetics ; Plant Proteins/immunology ; Plants, Genetically Modified/genetics ; Plants, Genetically Modified/immunology ; Protein Kinases/genetics ; Protein Kinases/immunology ; Proteins/immunology ; Receptors, Cell Surface/genetics ; Receptors, Cell Surface/immunology ; Nicotiana/genetics ; Nicotiana/immunology ; Transgenes
    Chemical Substances Plant Proteins ; Proteins ; Receptors, Cell Surface ; elicitin, Phytophthora ; Protein Kinases (EC 2.7.-)
    Language English
    Publishing date 2020-02-12
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 205723-2
    ISSN 1090-2104 ; 0006-291X ; 0006-291X
    ISSN (online) 1090-2104 ; 0006-291X
    ISSN 0006-291X
    DOI 10.1016/j.bbrc.2020.02.014
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Synthetic Peucedanocoumarin IV Prevents α-Synuclein Neurotoxicity in an Animal Model of Parkinson’s Disease

    Heejeong Kim / Han-Joo Maeng / Ji Hun Kim / Jin-Ha Yoon / Yohan Oh / Seung-Mann Paek / Yunjong Lee

    International Journal of Molecular Sciences, Vol 23, Iss 8618, p

    2022  Volume 8618

    Abstract: ... and protect dopaminergic neurons in Parkinson’s disease (PD). Here, we found that trans -4′-acetyl-3 ...

    Abstract Pathological protein inclusion formation and propagation are the main causes of neuronal dysfunction in diverse neurodegenerative diseases; therefore, current disease-modifying therapeutic strategies have targeted this disease protein aggregation process. Recently, we reported that peucedanocoumarin III (PCiii) is a promising therapeutic compound with the ability to disaggregate α-synuclein inclusion and protect dopaminergic neurons in Parkinson’s disease (PD). Here, we found that trans -4′-acetyl-3′-tigloylkhellactone (racemic peucedanocoumarin IV [PCiv]), a structural isomer of PCiii with a higher synthetic yield presented a strong anti-aggregate activity to a degree comparable to that of PCiii. PCiv retained effective inhibitory function against β-sheet aggregate-mimic β23 cytotoxicities and potently prevented α-synucleinopathy in α-synuclein preformed fibril (PFF)-treated mice cortical neurons. In detailed pharmacokinetic profiling of PCiv, oral administration of PCiv in rats exhibited an approximately 97-min half-life and 10% bioavailability. Moreover, tissue distribution analysis revealed favorable profiles of brain penetration with a 6.4 brain-to-plasma concentration ratio. The therapeutic efficacy of PCiv was further evaluated in a sporadic PD mouse model with a combinatorial co-injection of α-synuclein preformed fibril and recombinant adeno-associated virus expressing α-synuclein. Motor dysfunctions induced in this combinatorial α-synucleinopathy PD mouse model was almost completely rescued by PCiv diet administration, and this therapeutic effect is consistent with the marked prevention of dopaminergic neuron loss and suppression of α-synuclein aggregation. Taken together, our translational study suggests that PCiv is advantageous as a therapeutic agent for neurodegenerative diseases, especially with its good synthetic yield, high brain distribution, and anti-aggregate activity. PCiv may be useful in the management of α-synuclein inclusion formation and propagation at different stages of PD.
    Keywords peucedanocoumarin IV ; organic synthesis ; Parkinson’s disease ; pharmacokinetics ; α-synuclein preformed fibril ; dopaminergic cell loss ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Language English
    Publishing date 2022-08-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article: The inflammatory signature in monocytes of Sjögren’s syndrome and systemic lupus erythematosus, revealed by the integrated Reactome and drug target analysis

    Lee, Kyung Eun / Mun, Seyoung / Kim, Song-mi / Shin, Wonseok / Jung, Won / Paek, Joon / Lee, Jungnam / Hudson, Erin / Reeves, Wesley H. / Han, Kyudong / Cha, Seunghee

    Genes & genomics. 2022 Oct., v. 44, no. 10

    2022  

    Abstract: ... monocytes, is known to be critical in the pathogenesis of autoimmune Sjögren’s syndrome (SjS) and systemic ...

    Abstract BACKGROUND: The innate immune regulation, especially by the type I IFN signature in the CD14+ monocytes, is known to be critical in the pathogenesis of autoimmune Sjögren’s syndrome (SjS) and systemic lupus erythematosus (SLE). OBJECTIVE: Since patients with one condition can be overlapped with another, this study is to identify shared differentially expressed genes (DEGs) in SjS and SLE compared to healthy controls (HCs) and refine transcriptomic profiles with the integrated Reactome and gene-drug network analysis for an anti-inflammation therapy. METHODS: CD14+ monocytes were purified from whole blood of SjS and SLE patients (females, ages from 32 to 62) and subject to bulk RNA-sequencing, followed by data analyses for comparison with HC monocytes (females, ages 30 and 33). Functional categorizations, using Gene Ontology (GO) and the Reactome pathway analysis, were performed and DEGs associated with therapeutic drugs were identified from the Drug Repurposing Hub (DHUB) database. RESULTS: The GO analysis revealed that DEGs in the inflammatory response and the cellular response to cytokine were highly enriched in both conditions. A propensity toward M1 macrophage differentiation appears to be prominent in SjS while the Response to Virus was significant in SLE monocytes. Through the Reactome pathway analysis, DEGs in the IFN signaling and the cytokine signaling in immune system were most significantly enriched in both. Upregulation of NGF-induced transcription activity in SjS and the complement cascade activity in SLE were also noted. Multiple anti-inflammatory drugs, such as prostaglandin-endoperoxide synthase and angiotensin-I-converting- enzyme were associated with the DEGs in these conditions. CONCLUSIONS: Taken together, our analysis indicates distinct inflammatory transcriptomic profiles shared in SjS and SLE monocytes. Comprehensive characterizations of the data from these conditions will ultimately allow differential diagnosis of each condition and identification of therapeutic targets.
    Keywords complement ; cytokines ; drugs ; gene expression regulation ; gene ontology ; genomics ; inflammation ; lupus erythematosus ; macrophages ; monocytes ; pathogenesis ; prostaglandin synthase ; sequence analysis ; therapeutics ; transcriptomics ; viruses
    Language English
    Dates of publication 2022-10
    Size p. 1215-1229.
    Publishing place Springer Nature Singapore
    Document type Article
    ZDB-ID 2504587-8
    ISSN 2092-9293 ; 1976-9571
    ISSN (online) 2092-9293
    ISSN 1976-9571
    DOI 10.1007/s13258-022-01308-y
    Database NAL-Catalogue (AGRICOLA)

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  6. Article ; Online: Clinical outcome prediction from analysis of microelectrode recordings using deep learning in subthalamic deep brain stimulation for Parkinson`s disease.

    Kwang Hyon Park / Sukkyu Sun / Yong Hoon Lim / Hye Ran Park / Jae Meen Lee / Kawngwoo Park / Beomseok Jeon / Hee-Pyoung Park / Hee Chan Kim / Sun Ha Paek

    PLoS ONE, Vol 16, Iss 1, p e

    2021  Volume 0244133

    Abstract: ... for improving the motor symptoms of advanced Parkinson's disease (PD). Accurate positioning of the stimulation ...

    Abstract Background Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective treatment for improving the motor symptoms of advanced Parkinson's disease (PD). Accurate positioning of the stimulation electrodes is necessary for better clinical outcomes. Objective We applied deep learning techniques to microelectrode recording (MER) signals to better predict motor function improvement, represented by the UPDRS part III scores, after bilateral STN DBS in patients with advanced PD. If we find the optimal stimulation point with MER by deep learning, we can improve the clinical outcome of STN DBS even under restrictions such as general anesthesia or non-cooperation of the patients. Methods In total, 696 4-second left-side MER segments from 34 patients with advanced PD who underwent bilateral STN DBS surgery under general anesthesia were included. We transformed the original signal into three wavelets of 1-50 Hz, 50-500 Hz, and 500-5,000 Hz. The wavelet-transformed MER was used for input data of the deep learning. The patients were divided into two groups, good response and moderate response groups, according to DBS on to off ratio of UPDRS part III score for the off-medication state, 6 months postoperatively. The ratio were used for output data in deep learning. The Visual Geometry Group (VGG)-16 model with a multitask learning algorithm was used to estimate the bilateral effect of DBS. Different ratios of the loss function in the task-specific layer were applied considering that DBS affects both sides differently. Results When we divided the MER signals according to the frequency, the maximal accuracy was higher in the 50-500 Hz group than in the 1-50 Hz and 500-5,000 Hz groups. In addition, when the multitask learning method was applied, the stability of the model was improved in comparison with single task learning. The maximal accuracy (80.21%) occurred when the right-to-left loss ratio was 5:1 or 6:1. The area under the curve (AUC) was 0.88 in the receiver operating characteristic (ROC) curve. Conclusion Clinical improvements in PD patients who underwent bilateral STN DBS could be predicted based on a multitask deep learning-based MER analysis.
    Keywords Medicine ; R ; Science ; Q
    Subject code 610
    Language English
    Publishing date 2021-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: Therapeutic Evaluation of Synthetic Peucedanocoumarin III in an Animal Model of Parkinson’s Disease

    Sangwoo Ham / Heejeong Kim / Jin-Ha Yoon / Hyojung Kim / Bo Reum Song / Jeong-Yun Choi / Yun-Song Lee / Seung-Mann Paek / Han-Joo Maeng / Yunjong Lee

    International Journal of Molecular Sciences, Vol 20, Iss 21, p

    2019  Volume 5481

    Abstract: The motor and nonmotor symptoms of Parkinson’s disease (PD) correlate with the formation and ... Given these properties, the synthetic PCIII’s neuroprotective function was assessed in 6-hydroxydopamine (6-OHDA)-induced ...

    Abstract The motor and nonmotor symptoms of Parkinson’s disease (PD) correlate with the formation and propagation of aberrant α-synuclein aggregation. This protein accumulation is a pathological hallmark of the disease. Our group recently showed that peucedanocoumarin III (PCIII) possesses the ability to disaggregate β sheet aggregate structures, including α-synuclein fibrils. This finding suggests that PCIII could be a therapeutic lead compound in PD treatment. However, the translational value of PCIII and its safety information have never been explored in relevant animal models of PD. Therefore, we first designed and validated a sequence of chemical reactions for the large scale organic synthesis of pure PCIII in a racemic mixture. The synthetic PCIII racemate facilitated clearance of repeated β sheet aggregate (β23), and prevented β23-induced cell toxicity to a similar extent to that of purified PCIII. Given these properties, the synthetic PCIII’s neuroprotective function was assessed in 6-hydroxydopamine (6-OHDA)-induced PD mouse models. The PCIII treatment (1 mg/kg/day) in a 6-OHDA-induced PD mouse model markedly suppressed Lewy-like inclusions and prevented dopaminergic neuron loss. To evaluate the safety profiles of PCIII, high dose PCIII (10 mg/kg/day) was administered intraperitoneally to two-month-old mice. Following 7 days of PCIII treatment, PCIII distributed to various tissues, with substantial penetration into brains. The mice that were treated with high dose PCIII had no structural abnormalities in the major organs or neuroinflammation. In addition, high dose PCIII (10 mg/kg/day) in mice had no adverse impact on motor function. These findings suggest that PCIII has a relatively high therapeutic index. Given the favorable safety features of PCIII and neuroprotective function in the PD mouse model, it may become a promising disease-modifying therapy in PD to regulate pathogenic α-synuclein aggregation.
    Keywords peucedanocoumarin iii ; organic synthesis ; parkinson’s disease ; distribution ; α-synuclein aggregation ; dopaminergic cell loss ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Subject code 630
    Language English
    Publishing date 2019-11-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Conference proceedings: The role of 7.0T brain MRI in Parkinson’s disease

    Paek, Sun Ha

    2016  , Page(s) DI.12.07

    Event/congress 67. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), 1. Joint Meeting mit der Koreanischen Gesellschaft für Neurochirurgie (KNS); Frankfurt am Main; Deutsche Gesellschaft für Neurochirurgie; 2016
    Keywords Medizin, Gesundheit
    Publishing date 2016-06-08
    Publisher German Medical Science GMS Publishing House; Düsseldorf
    Document type Conference proceedings
    DOI 10.3205/16dgnc171
    Database German Medical Science

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  9. Article: CaLecRK-S.5, a pepper L-type lectin receptor kinase gene, accelerates Phytophthora elicitin-mediated defense response

    Woo, Joo Yong / Kim, Young Jin / Paek, Kyung-Hee

    Biochemical and biophysical research communications. 2020 Feb. 03,

    2020  

    Abstract: ... PAMPs) by pattern-recognition receptors (PRRs) located on the plant cell surface. CaLecRK-S.5, a pepper ... activation. To further elucidate the molecular mechanism of CaLecRK-S.5, transgenic tobacco plants were ... of CaLecRK-S.5, but this accumulation was completely abolished in homozygous transgenic plants ...

    Abstract Innate immunity in plants relies on the recognition of pathogen-associated molecular patterns (PAMPs) by pattern-recognition receptors (PRRs) located on the plant cell surface. CaLecRK-S.5, a pepper L-type lectin receptor kinase, has been shown to confer broad-spectrum resistance through priming activation. To further elucidate the molecular mechanism of CaLecRK-S.5, transgenic tobacco plants were generated in this study. Interestingly, hemizygous transgenic plants exhibited a high accumulation of CaLecRK-S.5, but this accumulation was completely abolished in homozygous transgenic plants by a cosuppression mechanism. Gain-of-function and loss-of-function analyses revealed that CaLecRK-S.5 plays a positive role in Phytophthora elicitin-mediated defense responses.
    Keywords Phytophthora ; RNA interference ; gain-of-function mutation ; genes ; homozygosity ; innate immunity ; lectins ; loss-of-function mutation ; pepper ; research ; tobacco
    Language English
    Dates of publication 2020-0203
    Publishing place Elsevier Inc.
    Document type Article
    Note NAL-AP-2-clean ; Pre-press version
    ZDB-ID 205723-2
    ISSN 0006-291X ; 0006-291X
    ISSN (online) 0006-291X
    ISSN 0006-291X
    DOI 10.1016/j.bbrc.2020.02.014
    Database NAL-Catalogue (AGRICOLA)

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  10. Article ; Online: Intrastriatal administration of coenzyme Q10 enhances neuroprotection in a Parkinson’s disease rat model

    Hyung Woo Park / Chun Gwon Park / Min Park / Seung Ho Lee / Hye Ran Park / Jaesung Lim / Sun Ha Paek / Young Bin Choy

    Scientific Reports, Vol 10, Iss 1, Pp 1-

    2020  Volume 12

    Abstract: Abstract Parkinson’s disease is a neurodegenerative disorder, and no treatment has been ... of Coenzyme Q10 could effectively prevent dopaminergic neuron degeneration. To this end, a Parkinson’s disease rat ... can be an effective strategy to prevent neurodegeneration in Parkinson’s disease. ...

    Abstract Abstract Parkinson’s disease is a neurodegenerative disorder, and no treatment has been yet established to prevent disease progression. Coenzyme Q10, an antioxidant, has been considered a promising neuroprotective agent; however, conventional oral administration provides limited efficacy due to its very low bioavailability. In this study, we hypothesised that continuous, intrastriatal administration of a low dose of Coenzyme Q10 could effectively prevent dopaminergic neuron degeneration. To this end, a Parkinson’s disease rat model induced by 6-hydroxydopamine was established, and the treatment was applied a week before the full establishment of this disease model. Behavioural tests showed a dramatically decreased number of asymmetric rotations in the intrastriatal Coenzyme Q10 group compared with the no treatment group. Rats with intrastriatal Coenzyme Q10 exposure also exhibited a larger number of dopaminergic neurons, higher expression of neurogenetic and angiogenetic factors, and less inflammation, and the effects were more prominent than those of orally administered Coenzyme Q10, although the dose of intrastriatal Coenzyme Q10 was 17,000-times lower than that of orally-administered Coenzyme Q10. Therefore, continuous, intrastriatal delivery of Coenzyme Q10, especially when combined with implantable devices for convection-enhanced delivery or deep brain stimulation, can be an effective strategy to prevent neurodegeneration in Parkinson’s disease.
    Keywords Medicine ; R ; Science ; Q
    Subject code 610
    Language English
    Publishing date 2020-06-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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