scholarly journals Sgt1 Regulates α-Synuclein Subcellular Localization and Expression of Parkinson’s Disease Related Genes, PINK1 and PARK9

Biomolecules ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 1675
Author(s):  
Anastasiia Bohush ◽  
Agnieszka Góral ◽  
Małgorzata Sierant ◽  
Barbara Nawrot ◽  
Wiesława Leśniak ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Protective Action ◽  
Subcellular Fractionation ◽  
Hek293 Cells ◽  
Immunofluorescent Staining ◽  
Mammalian Brain ◽  
Altered Level ◽  
Disease Related Genes ◽  
Insight Into

The SGT1 protein is highly expressed in the mammalian brain, particularly in neurons of the hippocampus and cortex, and in Purkinje cells of the cerebellum. There are literature data indicating that the protein may be involved in pathogenesis of neurodegenerative disorders such as Parkinson’s disease (PD). In the present work we have found that SGT1 protected cells from the toxicity of rotenone, an agent that evokes behavioral and histopathological symptoms of PD. To gain more insight into the possible mechanism underlying the protective action of SGT1 we looked at α-synuclein subcellular distribution in HEK293 cells with an altered SGT1 level. By immunofluorescent staining we have found that in HEK293 cells overexpressing SGT1 α-synuclein was mainly localized in the cytoplasm while in control cells it was present in the nucleus. Accordingly, when SGT1 expression was silenced, α-synuclein was predominantly present in the nucleus. These results were then confirmed by subcellular fractionation and Western blot analysis. Moreover, we have found that altered level of SGT1 in HEK293 cells influenced the expression of PD related genes, PINK1 and PARK9. Altogether, our results point to SGT1 as an important factor that might be involved in the pathogenesis of Parkinson’s disease (PD).

scholarly journals Interactions of COMT and ALDH2 Genetic Polymorphisms on Symptoms of Parkinson’s Disease

2021 ◽  
Vol 11 (3) ◽  
pp. 361
Author(s):  
Rwei-Ling Yu ◽  
Shao-Ching Tu ◽  
Ruey-Meei Wu ◽  
Pei-An Lu ◽  
Chun-Hsiang Tan
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Detrimental Effect ◽  
Personal Hygiene ◽  
Nucleotide Polymorphisms ◽  
Monoamine Neurotransmitters ◽  
Single Nucleotide ◽  
Detrimental Impact ◽  
Reduced Activity ◽  
Insight Into

(1) Background: Monoamine neurotransmitters play essential roles in the normal functioning of our nervous system. However, the metabolism of monoamine neurotransmitters is accompanied by the production of neurotoxic metabolites, and inefficient removal of the metabolites has been suggested to cause neurodegeneration. (2) Methods: To examine the effect of reduced activity of catechol-O-methyltransferase (COMT) and aldehyde dehydrogenase 2 (ALDH2) conferred by single nucleotide polymorphisms COMT rs4680(A) and ALDH2 rs671(A) on the symptoms of patients with Parkinson’s disease (PD), a total of 114 PD patients were recruited cross-sectionally and received genotyping for rs4680 and rs671 along with MDS-UPDRS evaluation. (3) Results: We found that patients carrying rs4680(A) had more severe bradykinesia in the upper extremity and rest tremor. Besides, patients carrying rs671(A) had more difficulty maintaining personal hygiene, while patients with genotype rs671(GG) had higher scores in the item “depressed mood.” More importantly, we found the effect of rs4680 to be moderated by rs671 SNP for the symptom of “hand movements.” The detrimental impact of rs4680(A) is more pronounced in the presence of genotype rs671(GG). (4) Conclusions: This study facilitates a deeper understanding of the detrimental effect of reduced activity of COMT and ALDH2 conferred by genetic variation and provides novel insight into the interactions between enzymes metabolizing monoamine neurotransmitters in the pathogenesis of PD.

scholarly journals A selective effect of dopamine on information-seeking

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Valentina Vellani ◽  
Lianne P de Vries ◽  
Anne Gaule ◽  
Tali Sharot
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Information Seeking ◽  
Selective Effect ◽  
Reward Seeking ◽  
The Impact ◽  
The Brain ◽  
Insight Into ◽  
Primary Reward

Humans are motivated to seek information from their environment. How the brain motivates this behavior is unknown. One speculation is that the brain employs neuromodulatory systems implicated in primary reward-seeking, in particular dopamine, to instruct information-seeking. However, there has been no causal test for the role of dopamine in information-seeking. Here, we show that administration of a drug that enhances dopamine function (dihydroxy-L-phenylalanine; L-DOPA) reduces the impact of valence on information-seeking. Specifically, while participants under Placebo sought more information about potential gains than losses, under L-DOPA this difference was not observed. The results provide new insight into the neurobiology of information-seeking and generates the prediction that abnormal dopaminergic function (such as in Parkinson’s disease) will result in valence-dependent changes to information-seeking.

scholarly journals Pilot Study of Mindfulness Training on the Self-Awareness of Motor Symptoms in Parkinson’s Disease – A Randomized Controlled Trial

2021 ◽  
Vol 12 ◽  
Author(s):  
Timo Marcel Buchwitz ◽  
Franziska Maier ◽  
Andrea Greuel ◽  
Franziska Thieken ◽  
Kenan Steidel ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Control Group ◽  
Motor Symptoms ◽  
Self Awareness ◽  
Disease Symptoms ◽  
Waitlist Control ◽  
Sleeping Problems ◽  
Waitlist Control Group ◽  
Insight Into

Objective: This study aims to evaluate feasibility and effects of a newly developed mindfulness intervention tailored to specific needs of patients with Parkinson’s disease (PD).Background: The phenomenon of impaired self-awareness of motor symptoms (ISAm) in PD might be reduced by increasing patients’ mindfulness. A PD-specific mindfulness intervention has been developed and evaluated as a potential treatment option: IPSUM (“Insight into Parkinson’s Disease Symptoms by using Mindfulness”).Methods: IPSUM’s effectiveness is evaluated by comparing an intervention with a waitlist-control group. Applying a pre-post design, patients were assessed before, directly after and 8weeks after treatment. The primary outcome was the change in a quantitative ISAm score from baseline to post-assessment. Secondary outcome measures were PD-related affective changes and neuropsychological test performance. Feasibility was evaluated via feedback forms.Results: In total, 30 non-depressed and non-demented PD patients were included (intervention: n=14, waitlist-control: n=16). ISAm score did not change significantly, but the training group showed greater performance in sustained attention and language tasks over time. Additional changes included greater mindfulness as well as less sleeping problems and anxiety. Cognitive disturbances, apathy, and sleeping problems worsened only in the waitlist-control group. Patients’ feedback regarding the training concept and material was excellent.Conclusion: Insight into Parkinson’s Disease Symptoms by using Mindfulness has not been capable of reducing ISAm in PD patients but appears to be a feasible and effective concept to, among others, support mental health in the mid-term. It has to be noted though that the study was stopped beforehand because of the SARS CoV-2 pandemic. The lack of findings might therefore be caused by a lack of statistical power. The need for further research to better understand the mechanisms of ISAm and its connection to mindfulness in PD is highlighted.

scholarly journals Subsecond dopamine fluctuations in human striatum encode superposed error signals about actual and counterfactual reward

2015 ◽  
Vol 113 (1) ◽  
pp. 200-205 ◽  
Author(s):  
Kenneth T. Kishida ◽  
Ignacio Saez ◽  
Terry Lohrenz ◽  
Mark R. Witcher ◽  
Adrian W. Laxton ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Decision Making ◽  
Parkinson's Disease ◽  
Animal Models ◽  
Large Body ◽  
Reward Processing ◽  
Dopamine Neurons ◽  
Model Organisms ◽  
Mammalian Brain ◽  
Prediction Errors

In the mammalian brain, dopamine is a critical neuromodulator whose actions underlie learning, decision-making, and behavioral control. Degeneration of dopamine neurons causes Parkinson’s disease, whereas dysregulation of dopamine signaling is believed to contribute to psychiatric conditions such as schizophrenia, addiction, and depression. Experiments in animal models suggest the hypothesis that dopamine release in human striatum encodes reward prediction errors (RPEs) (the difference between actual and expected outcomes) during ongoing decision-making. Blood oxygen level-dependent (BOLD) imaging experiments in humans support the idea that RPEs are tracked in the striatum; however, BOLD measurements cannot be used to infer the action of any one specific neurotransmitter. We monitored dopamine levels with subsecond temporal resolution in humans (n = 17) with Parkinson’s disease while they executed a sequential decision-making task. Participants placed bets and experienced monetary gains or losses. Dopamine fluctuations in the striatum fail to encode RPEs, as anticipated by a large body of work in model organisms. Instead, subsecond dopamine fluctuations encode an integration of RPEs with counterfactual prediction errors, the latter defined by how much better or worse the experienced outcome could have been. How dopamine fluctuations combine the actual and counterfactual is unknown. One possibility is that this process is the normal behavior of reward processing dopamine neurons, which previously had not been tested by experiments in animal models. Alternatively, this superposition of error terms may result from an additional yet-to-be-identified subclass of dopamine neurons.

Favorite Activity Interview as a Window into the Identity of People with Parkinson's Disease

2006 ◽  
Vol 26 (2) ◽  
pp. 56-68 ◽  
Author(s):  
Emily J. DeGroat ◽  
Kathleen Doyle Lyons ◽  
Linda Tickle-Degnen
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Occupational Therapy ◽  
Personal Identity ◽  
Exploratory Study ◽  
Verbal Communication ◽  
Activity Participation ◽  
Verbal Content ◽  
Identity Expression ◽  
Insight Into

The purpose of this study was to document the degree to which a brief segment of an occupational therapy interview about favorite activities served as a window into personal identity and experience in clients with Parkinson's disease. Two-minute segments of videotaped interviews of 12 participants with Parkinson's disease were transcribed and analyzed. A verbal content measure was developed, its reliability tested, and its items correlated with participants' self-rated personality and mood. Overall, the inter-rater reliability for this verbal content measure was acceptably high, and many expected associations between participant verbal content and participant identity as related to personality and mood were found. The results tentatively suggest that the client's discussion of favorite activity participation, as well as the tone and frequency of the client's verbal communication, can provide insight into the identity of the client, and this information is available to the practitioner even for clients who have difficulty expressing their identities nonverbally. This exploratory study establishes a foundation for further research in the area of identity expression through verbal content in individuals with diminished nonverbal expressiveness.

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