: Background: Parkinson’s disease (PD) is a chronic, progressive illness with a profound impact on health-related quality of life, and it is crucial to know what factors influence quality of life throughout the course of the disease. This study aimed to evaluate PD patients’ motor and non-motor symptoms to compare symptom severity between PD clinical phenotypes and to assess the impact of disease symptoms on quality of life in a cohort of Latvian patients. Methods: We evaluated 43 patients with Parkinson’s disease. Fourteen patients had tremor-dominant (TD) PD, twenty-five patients had postural instability/gait difficulty (PIGD), and four patients had a mixed phenotype. Results: The patients’ mean age was 65.21 years, and the disease’s mean duration was 7 years. The most common non-motor symptoms were fatigue (95.3%), sleep disturbance (83.7%), daytime sleepiness (83.7%), and pain and other sensations (81.4%). PIGD patients had a higher prevalence of depressed mood, daytime sleepiness, constipation, light headedness on standing, cognitive impairment, and severe gastrointestinal and urinary disturbances (as assessed using the SCOPA-AUT domains) compared with TD patients. A high prevalence of fatigue was assessed in both disease subtypes. Health-related quality of life significantly statistically correlated with MDS-UPDRS parts III and IV (r = 0.704), the Hoehn and Yahr scale (r = 0.723), as well as the SCOPA-AUT scale’s gastrointestinal (r = 0.639), cardiovascular (r = 0.586), thermoregulatory (r = 0.566) and pupillomotor domains (r = 0.597). Conclusion: The severity of motor symptoms, as well as non-motor symptoms, such as fatigue, apathy, sleep problems and daytime sleepiness, pain, and disturbances in gastrointestinal and cardiovascular function, negatively affect PD patients’ health-related quality of life. Thermoregulatory and pupillomotor symptoms also significantly affect PD patients’ well-being.

Background: Parkinsons’s disease is characterized by progressive worsening of gait, posture and balance with disability in daily life activities and to improvement in chronic musculoskeletal pain, often in neck pain associated with worsening of balance. The aim of the study is to investigate the correlation between scoliosis, balance and cervical pain in Parkinson’s disease. Methods: Cross-sectional, pilot study. A total of 16 Parkinson’s patients were enrolled in the study. The Pain Visual analogue scale and the short form McGill pain questionnaire measured neck cervical pain; static balance, Tinetti, Berg Balance and Short Physical Performance Battery scales(SPPB) were used to evaluate dynamic balance. Whole-spine standard X-ray assess spinal scoliosis with Cobb angles measurement .An observational statistical analysis was performed with the patients subdivided into a non-scoliosis (NS) group and a true scoliosis (TS) group based on whether they presented a Cobb’s angle below or ≥10°. Results: Frequency of neck pain in the NS group was 37% compared to 50% in the TS group. A non-statistically significant difference was found in terms of static, dynamic balance and cervical pain scores between NS and TS groups. Conclusions: Scoliosis, cervical pain and postural imbalance are significant yet often overlooked complaints in PD.

The phenomenon of decreased serum uric acid (UA) levels in patients with Parkinson’s disease (PD) and its relationship with purine metabolic pathways remain unclear. We compared inosine, hy-poxanthine, xanthine, and UA levels in serum and cerebrospinal fluid (CSF) of PD patients with those of controls, and investigated the effect of changes in the purine metabolic system on UA levels in PD. Overall, 134 samples (serum, 45 PD patients and 30 controls; CSF, 39 PD patients and 20 controls), were analyzed using liquid chromatography-tandem mass spectrometry. A general linear model (GLM) was used to investigate relationships among purine metabolites. Compared to controls, PD patients had significantly lower UA levels in the serum and CSF, and serum and CSF UA levels were significantly correlated. Additionally, in PD, decreased serum hypoxanthine levels were observed with decreased CSF inosine and hypoxanthine levels, suggesting the involvement of the purine recycling system. GLM analysis indicated that the reduced UA levels in PD were mainly due to sources other than the purine metabolic system, such as exercise, nutritional indices, muscle volume, or adipose tissue. Our results highlight the impairment of purine recycling pathways in PD, as evidenced by the decreased serum hypoxanthine and CSF inosine.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the loss of dopamin-ergic neurons responsible for unintended or uncontrollable movements. Mutations in leu-cine-rich repeat kinase 2 locus, contributes to genetic forms of PD. The fruit fly Drosophila mela-nogaster carrying this mutation (LRRK2-Dm), is an in vivo model of PD that develops motor impairment and stands for an eligible non mammalian paradigm to test novel therapeutic ap-proaches. Dehydrozingerone (DHZ) is a natural phenolic compound isolated from ginger. Pre-sents anti-inflammatory, antioxidant and neuroprotective properties making it a potential therapeutic target for PD. We administered DHZ and its C2-symmetric dimer (DHZ-DIM) at 0.5 and 1mM, for 14 and 21 days, in the LRRK2-Dm, with the aim to assess changes for rescuing motor behavior, brain dopaminergic neurons, mitochondria and synapses (T-Bars). The shorter treat-ment with both molecules revealed efficacy at the higher dose improving climbing behavior with a prevention of dopaminergic neuronal demise. After 21 days, a recovery of the motor disability, dopaminergic neuron loss, mitochondrial damage and T-Bars failure was observed with the DHZ-DIM. Our data indicates that the DHZ-DIM exerts a more potent neuroprotective effect respect to the monomer in LRRK2-Dm, prompting further investigation of these compounds in rodent models of PD.

Parkinson’s Disease (PD) is a neurodegenerative and progressive disease that impacts the nerve cells in the brain and varies from person to person. The exact cause of PD is still unknown, and the diagnosis of PD does not include a specific objective test with certainty. Although deep learning has made great progress in medical neuroimaging analysis, these methods are very susceptible to biases present in neuroimaging datasets. An innovative decorrelated deep learning technique is introduced to mitigate class bias and scanner bias while simultaneously focusing on finding distinguishing characteristics in resting-state functional MRI (rs-fMRI) data, which assist in recognizing the PD with good accuracy. The decorrelation function reduces the non-linear correlation between features and bias in order to learn bias-invariant features. The Parkinson’s Progression Markers Initiative (PPMI) dataset, referred to as a single scanner imbalanced dataset in this study used to validate our method. The imbalanced dataset problem affects the performance of the deep learning framework by overfitting to the majority class. To resolve this problem, we propose a new Decorrelated Convolutional Neural Networks (DcCNN) framework by applying decorrelation-based optimization to Convolutional Neural Networks(CNN). An analysis of evaluation metrics comparisons shows that integrating the decorrelation function boosts the performance of PD recognition by removing class bias. Specifically, our DcCNN model performs significantly better than existing traditional approaches to tackle the imbalance problem. Finally, the same framework can be extended to create scanner invariant features without significantly impacting the performance of a model. The obtained dataset is a multi-scanner dataset which leads to scanner bias due to the differences in acquisition protocols and scanners. The multi-scanner dataset is a combination of two datasets, namely PPMI and FTLDNI - frontotemporal lobar degeneration neuroimaging initiative (NIFD) dataset. The results of t-distributed stochastic neighbor embedding (t-SNE) and scanner classification accuracy of our proposed Feature Extraction-DcCNN (FE-DcCNN) model validated the effective removal of scanner bias. Our method achieves an average accuracy of 77.80% on a multi-scanner dataset for differentiating PD from healthy control, which is superior to the DcCNN model trained on a single scanner imbalanced dataset.

The present exploratory study tested the hypothesis that computerized cognitive training (CCT) in home telemonitoring may beneficially affect eyes-closed resting-state electroencephalographic (rsEEG) rhythms in Parkinson's disease patients with cognitive deficits (PDCD). A Eurasian database provided clinical-demographic-rsEEG datasets in 40 PDCD patients, 29 PD patients without cognitive deficits (PDNCD), 40 Alzheimer’s disease patients with cognitive deficits (ADCD), and 40 cognitively normal older adults (Healthy). Sixteen of the 40 PDCD patients completed a cross-over unsupervised CCT program of simple, serious video games (versus a sham program) consisting of 14 daily sessions of approximately 20 minutes each in the patients' homes. Compared to the Healthy, PDNCD, and ADCD groups, the PDCD group was characterized by greater diffuse rsEEG delta (about 2-4 Hz) and theta (about 4-7 Hz) source activity. The PDCD patients who underwent the CCT program showed an improvement in video game performance and a reduction in these delta-theta source activities after this program compared to the control condition. In conclusion, these results suggest that the 2-week CCT program in home telemonitoring may mitigate the abnormal “slowing” of rsEEG rhythms in PDCD patients, possibly enhancing the regulation of brain arousal and quiet vigilance.

4-(2-Methyloxazol-4-yl)benzenesulfonamide was synthesized by the reaction of 4-(2-bromoacetyl)benzenesulfonamide with an excess of acetamide. The obtained compound was evaluated as a potential inhibitor of human monoamine oxidase (MAO) A and B and was found to inhibit these enzymes with IC50 values of 3.47 μM for MAO-B and 43.3 μM for MAO-A. Thus, the new selective MAO-B inhibitor was identified, which may be used as the lead compound for development anti-Parkinson’s disease agents.

Early detection of cognitive decline and in-time non-pharmacological management or drug therapy are extremely important in providing care for Parkinson’s disease with dementia (PDD). In this study, we firstly conducted a discovery study to identify 6 plasma microRNAs that may differentiate PD with or without mild cognitive impairment via NGS sequencing. Total 120 participants were further recruited in validation cohort and divided into 4 subgroups, including normal controls (HC), PD with no dementia (PDND), PD with mild cognitive impairment (PD-MCI) and PDD. Among the 6 candidates, miR-203a-3p was successfully detected in the plasma of the validation cohort using droplet digital PCR (ddPCR). Our results showed that the ratio of miR-203a-3p/miR-16-5p observed in PDD was significantly increased compared to PD-MCI (p < 0.001) and PDND (p = 0.041). Moreover, the ratio of miR-203a-3p/miR-16-5p showed a significant correlation with MoCA scores (r = -0.237, p = 0.024) in patients with PD (PwP). The ROC curve of the logistic regression model, consisting variates of age, the ratio of miR-203a-3p/miR-16-5p and the score of UPDRS III, also demonstrated an average AUC of 0.883 by 5-fold cross-validation. In conclusion, the ratio of miR-203a-3p/miR-16-5p may serve as a potential biomarker for distinguishing cognitive dysfunction from PwP.

Oxidative stress-mediated cell death is a major cause of dopaminergic neuronal loss in the substantia nigra (SN) of Parkinson’s disease patients. Ergothioneine (ET), a natural dietary compound, has been shown to have cytoprotective functions, but neuroprotective actions against PD have not been well established. 6-Hydroxydopamine (6-OHDA) is a widely used neurotoxin to simulate the degeneration of dopaminergic (DA) neurons in Parkinson's disease. In this study, we investigated the protective effect of ET on 6-OHDA treated iPSC-derived dopaminergic neurons (iDAs) and further confirmed the protective effects in 6-OHDA treated human neuroblastoma SH-SY5Y cells. In 6-OHDA treated cells, metabolic stress in the form of decreased mitochondrial membrane potential (ΔΨm), increased mitochondrial reactive oxygen species (mROS), reduced cellular ATP levels, and increased total protein carbonylation levels was observed. 6-OHDA treatment also significantly decreased tyrosine hydroxylase levels. These effects were significantly abrogated when ET was present. Verapamil hydrochloride (VHCL), a non-specific inhibitor of the ET transporter, OCTN1, abolished ET’s cytoprotective effects, indicative of an intracellular action. These results suggest that ET could be a potential therapeutic for Parkinson’s disease.

In this work, we explore the intrinsic disorder status of the three members of the synuclein family of proteins - α-, β-, and γ-synucleins. We also analyzed the peculiarities of the amino acid sequences and modeled 3D structures of the human synuclein family members to find potential effects of pathological mutations. Furthermore, we conducted a comparative sequence-based analysis of the synuclein proteins from various evolutionary distant species and evaluated their levels of intrinsic disorder using a set of commonly used bioinformatics tools. Next, we conducted a detailed functional disorder analysis of the proteins in the interactomes of the human synuclein family members using various web-based disorder analysis and prediction tools, such as RIDAO, D2P2 and FuzDrop. We identify that the interactome of human α-synuclein has relatively higher levels of intrinsic disorder, as compared to the interactomes of human β- and γ- synucleins. These observations highlight the critical importance of intrinsic disorder of human α-synuclein and its interactors in neuronal processes as compared to other proteins of the synuclein family.

Introduction: Parkinson’s disease (PD) patients harboring recessive gene variants exhibit a distinct clinical phenotype with an early disease onset and relatively mild symptoms. Data concerning individualized therapy for autosomal recessive PD forms are still scarce. Methods: Demographic and treatment data of a cohort of PD carriers of recessive genes (9 homozygous or compound heterozygous PRKN carriers, 4 Heterozygous PRKN carriers and 3 biallelic PINK1 carriers) were evaluated. Results: The average Levodopa Equivalent daily dose (LEDD) was 806.8±453.5 (range 152-1810) in PRKN carriers and 765±96.6 (range 660-850) in PINK1 carriers. The majority responded to low/moderate doses of Levodopa. The response to Dopamine Agonists (DA) was often favorable both as initial and longitudinal therapy. 8/13 PRKN and 1/3 PINK1 carriers were treated with amantadine successfully, and this also applied to patients who could not tolerate Levodopa or DA. Conclusions: In the era of personalized treatment, the therapeutic approach in recessive PD gene carriers might differ as compared to idiopathic PD. Lower LEDD doses were efficient even in patients with a very long disease duration, while a few patients were doing well without any Levodopa treatment decades after disease initiation. DA or amantadine could be used as a first and main line treatment regimen if well tolerated. Literature data on therapeutic strategies in carriers of pathogenic mutations in recessive PD genes, including device-aided treatments will be further discussed.

Parkinson's disease (PD) is recognized as the second most prevalent primary chronic neurodegenerative disorder of the central nervous system. Clinically, PD is characterized as a movement disorder, exhibiting an incidence and mortality rate that is increasing faster than any other neurological condition. In recent years, there has been a growing interest concerning the role of the gut microbiome in the etiology and pathophysiology of PD. The establishment of a brain-gut microbiome axis is now real, with evidence denoting a bidirectional communication between the brain and the gut microbiota through metabolic, immune, neuronal, and endocrine mechanisms and pathways. Among these, the vagus nerve represents the most direct form of communication between the brain and the gut. Given the potential interactions between bacteria and drugs, it has been observed that the therapies for PD can have an impact on the composition of the microbiome. Therefore, in the scope of the present review, we will discuss the current understanding of gut microbiome on PD and whether this may be a new paradigm for treating this devastating disease.