Neuro4PD: An Initial Neurorobotics Model of Parkinson's Disease.
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ABSTRACT:
SUBMITTER: Pimentel JM
PROVIDER: S-EPMC8283825 | biostudies-literature | 2021
REPOSITORIES: biostudies-literature
Publications
Neuro4PD: An Initial Neurorobotics Model of Parkinson's Disease.
Pimentel Jhielson M JM Moioli Renan C RC de Araujo Mariana F P MFP Ranieri Caetano M CM Romero Roseli A F RAF Broz Frank F Vargas Patricia A PA
Frontiers in neurorobotics 20210701
In this work, we present the first steps toward the creation of a new neurorobotics model of Parkinson's Disease (PD) that embeds, for the first time in a real robot, a well-established computational model of PD. PD mostly affects the modulation of movement in humans. The number of people suffering from this neurodegenerative disease is set to double in the next 15 years and there is still no cure. With the new model we were capable to further explore the dynamics of the disease using a humanoid ...[more]
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Project description:Early onset Parkinson’s Disease (onset <50 years) accounts for between 10-20 percent of all patients. While some of these cases are associated with specific mutations, the majority are sporadic where the cause is unknown. We generated induced pluripotent stem cells from sporadic early onset patients and differentiated them to dopamine neurons. At early stages in culture (30 days) we found significant elevations in soluble α-synuclein protein levels when compared to controls. This was associated with reductions in lysosomal membrane proteins such as LAMP1 and an increase in phosphorylated protein kinase C-α (p-PKCα). Testing activators of lysosomal function showed that specific phorbal esters reduced both α-synuclein and p-PKCα levels and increased LAMP1 expression. Interestingly, very low doses of the drug PEP005 were able to reduce α-synuclein levels without affecting p-PKCα. Similar effects of PEP005 on α-synuclein expression were seen following infusion into the mouse brain. Our data show that early onset sporadic Parkinson’s Disease can be accurately predicted using a ratio of α-synuclein and p-PKCα in dopamine neural cultures derived from patient iPSC’s and that specific phorbal esters can alter both biomarkers making these drugs promising candidates to treat Parkinson’s Disease.
2019-12-06 | PXD011326 | Pride
Project description:IntroductionSeveral treatment guidelines for Parkinson's disease (PD) had been proposed in recent decades. The aim of current study was to investigate the initial medication utilized in newly diagnosed PD subjects in Taiwan during an eleven-year period.MethodsA total of 7,550 patients with newly diagnosed Parkinsonism were retrospectively enrolled from the National Health Insurance Research Database of Taiwan from 2000 to 2010. After excluding patients at risk of secondary or atypical Parkinsonism, those never receiving medication or having incomplete data, 1,645 subjects were included. The participants were then divided into four treating regimen groups, namely levodopa (LD) only group, dopamine agonist (DA) only group, LD+DA group, and No-LD, No-DA group. The demographic data and medication retention rate were compared across the four treatment groups.ResultsLD only and No-LD, No-DA regimens were the main initial choice of PD treatment in Taiwan. LD containing drugs were more often prescribed to the elderly population than the other two treatment regimens, while No-LD, No-DA medication was the major initial choice for younger patients. DA only regimen occupied only 3-4% of the initial PD prescriptions and was given predominantly by neurologists. Over the eleven-year period, there is a trend for the middle-aged population to receive medication containing LD as initial treatment. The one year retention rate of anti-Parkinsonism medication was around 30-50% in our population. Age, polypharmacy, change of one-year daily levodopa equivalent dosage and newly onset of dementia, stroke and psychiatric diseases all affect drug compliance in PD patients.ConclusionsThis is the first long-term study to explore initial pharmacotherapies in an Asian PD population. We hope to provide evidence for adjusting government policies and public education of physicians and PD patients in the future.
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Project description:Background: Deep Brain Stimulation (DBS) is an underutilized surgical therapy for Parkinson's Disease (PD). Both physician and patient hesitancies have been described as potential barriers to DBS, but the specifics of patient perceptions of DBS have not been well-characterized in the general PD population. Objective: To characterize the understanding and impressions of surgical therapy in PD patients prior to formal surgical evaluation. Methods: A 30-question survey assessing impressions of surgical therapy for PD and understanding of DBS for PD was administered to PD patients seen at an urban movement disorders clinic. Results: One hundred and two patients completed the survey. When asked if they would undergo a hypothetical risk-free, curative brain surgery for PD, 98 patients responded "yes." Patients were more agreeable to "reversible," "minimally-invasive," and "incisionless" surgery. 51.2% thought DBS is an "effective" treatment for PD, 76.6% thought it was "invasive," and 18.3% thought it was "reversible." 45.2% reported fear of being awake during DBS surgery. Regarding costs, 52.4% were concerned that DBS was "very expensive" or "not covered by insurance." Initial source of information and perceived treatment effectiveness were not associated with concerns about DBS effectiveness or threats to normality. Negative perceptions of past surgery were associated with concerns about DBS altering mood and personality. Conclusion: Overall, patients expressed concerns regarding procedural efficacy, invasiveness, cost, and irreversibility-independent of the original source of information. Future studies are required to allow us to better understand the impact of these initial findings on DBS hesitancy and underutilization.
| S-EPMC7970030 | biostudies-literature
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| S-EPMC8246975 | biostudies-literature
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Project description:Parkinson's disease is the second most prevalent neurodegenerative disorder, characterized by the degeneration of dopaminergic neurons. Significant improvements in gait balance, particularly step length and velocity, were revealed by less-invasive wireless cortical stimulation. Transcriptome sequencing was performed to demonstrate the cellular mechanism, specifically targeting the primary motor cortex where the stimulation was applied. Our findings indicated that the differentially expressed genes (DEGs), initially down-regulated following Parkinson's disease induction, were subsequently restored to normal levels after cortical stimulation. We propose these DEGs as a potential target for motor disorder treatment in Parkinson's disease. These genes are implicated in crucial processes such as astrocyte-mediated blood vessel development and microglia-mediated phagocytosis of damaged motor neurons, suggesting their significant roles in improvement of behavior disorder. Moreover, these biomarkers not only facilitate rapid and accurate diagnosis of Parkinson's disease but also assist precision medicine approaches.
2024-07-11 | GSE271930 | GEO
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2009-09-23 | E-GEOD-4773 | biostudies-arrayexpress
Project description:Cellular toxicities of alpha-synuclein manifest through multiple pathways, including mitochondrial dysfunction and the inhibition of vesicle trafficking. Several defects can be ameliorated by small molecule suppressors that antagonize toxicity in model systems ranging from yeast to neurons. Connections between these distinct pathologies may be central to Parkinson Disease and to therapeutic strategies. First, yeast cultures with 1 or 2 copies of human alpha-synuclein were profiled during a time series of 0 to 6 hours. Second, to investigate any potential rescue of alpha-synuclein toxicity, one of a series of six compounds: compound 1 ((4-(3-iodophenyl)-3,4-dihydrobenzo[h]quinolin-2(1H)-one); compound 2 (4-(3-bromophenyl)-3,4-dihydrobenzo[h]quinolin-2(1H)-one); compound 3 (4-(5-bromo-2-fluorophenyl)-6,7-dimethyl-3,4-dihydro-2(1H)-quinolinone); compound 4 (4-(3-bromo-4-fluorophenyl)-6,7-dimethyl-3,4-dihydro-2(1H)-quinolinone); compound 5 (4-(4-ethyl)-6,7-dimethyl-3,4-dihydro-2(1H)-quinolinone); compound 6 ((4R)-6-bromo-4-(4-ethylphenyl)-3,4-dihydrobenzo[h]quinolin-2(1H)-one); was introduced and the expression profile assayed at 4 hours.
2010-01-04 | GSE11633 | GEO