Amino acids play numerous roles in the central nervous system, serving as neurotransmitters, neuromodulators and regulators of energy metabolism. The free amino acid profile in serum of Parkinson’s disease (PD) patients may be influenced by neurodegeneration, mitochondrial dysfunction, malabsorption in the gastroenteric tract and received treatment. The aim of our study was the evaluation of the profile of amino acid concentrations against disease progression. We assessed the amino acid profile in the serum of 73 patients divided into groups with early PD, late PD with dyskinesia and late PD without dyskinesia. Serum amino acid analysis was performed by high-pressure liquid chromatography with fluorescence detection. We observed some significant differences amongst the groups with respect to concentrations of alanine, arginine, phenylalanine and threonine, although no significant differences were observed between patients with advanced PD with and without dyskinesia. We conclude that this specific amino acid profile could serve as biochemical marker of PD progression.

Parkinson’s disease (PD), dementia with Lewy body (DLB), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD) and multiple system atrophy (MSA) belong to a group of neurodegenerative diseases called parkinsonian syndromes. They share several clinical, neuropathological and genetic features. Neurodegenerative diseases are characterized by the progressive dysfunction of specific populations of neurons, determining clinical presentation. Neuronal loss is associated with extra- and intracellular accumulation of misfolded proteins. The parkinsonian diseases affect distinct areas of the brain. PD and MSA belong to a group of synucleinopathies that are characterized by the presence of fibrillary aggregates of α-synuclein protein in the cytoplasm of selected populations of neurons and glial cells. PSP is a tauopathy associated with the pathological aggregation of the microtubule associated tau protein. Although PD is common in the world’s aging population and has been extensively studied, the exact mechanisms of the neurodegeneration are still not fully understood. Growing evidence indicates that parkinsonian disorders to some extent share a genetic background, with two key components identified so far: the microtubule associated tau protein gene (MAPT) and the α-synuclein gene (SNCA). The main pathways of parkinsonian neurodegeneration described in the literature are the protein and mitochondrial pathways. The factors that lead to neurodegeneration are primarily environmental toxins, inflammatory factors, oxidative stress and traumatic brain injury.

Background: Subthalamic nucleus deep brain stimulation (STN-DBS) has been an established method in improvement of motor disabilities in Parkinson's disease (PD) patients. It has been also claimed to have an impact on balance and gait disorders in PD patients, but the previous results are conflicting. Objective: The aim of this prospective controlled study was to evaluate the impact of STN-DBS on balance disorders in PD patients in comparison with Best-Medical-Therapy (BMT) and Long-term-Post-Operative (POP) group. Methods: DBS-group consisted of 20 PD patients (8F, 12M) who underwent bilateral STN DBS. POP-group consisted of 14 post-DBS patients (6F, 8M) in median 30 months-time after surgery. Control group (BMT-group) consisted of 20 patients (11F, 9M) who did not undergo surgical intervention. UPDRS III scale and balance tests (Up And Go Test, Dual Task- Timed Up And Go Test, Tandem Walk Test) and posturography parameters were measured during 3 visits in 9 ± 2months periods (V1, V2, V3) 4 phases of treatment (BMT-ON/OFF, DBS-ON/OFF). Results: We have observed the slowdown of gait and postural instability progression in first 9 post-operative months followed by co-existent enhancement of balance disorders in next 9-months evaluation (p < 0.05) in balance tests (Up and Go, TWT) and in posturography examination parameters (p < 0.05). The effect was not observed neither in BMT-group nor POP-group (p > 0.05): these groups revealed constant progression of static and dynamic instability (p > 0.05). Conclusions: STN-DBS can have modulatory effect on static and dynamic instability in PD patients: it can temporarily improve balance disorders. mainly during first 9 post-operative months, but with possible following deterioration of the symptoms in next post-operative months.

Parkinson’s disease (PD) is generally considered a sporadic disorder, but a strong genetic background is often found. The aim of this study was to identify the underlying genetic cause of PD in two affected siblings and to subsequently assess the role of mutations in Cathepsin B (CTSB) in susceptibility to PD. A typical PD family was identified and whole-exome sequencing was performed in two affected siblings. Variants of interest were validated using Sanger sequencing. CTSB p.Gly284Val was genotyped in 2077 PD patients and 615 unrelated healthy controls from the Czech Republic, Ireland, Poland, Ukraine, and the USA. The gene burden analysis was conducted for the CTSB gene in an additional 769 PD probands from Mayo Clinic Florida familial PD cohort. CTSB expression and activity in patient-derived fibroblasts and controls were evaluated by qRT-PCR, western blot, immunocytochemistry, and enzymatic assay. The CTSB p.Gly284Val candidate variant was only identified in affected family members. Functional analysis of CTSB patient-derived fibroblasts under basal conditions did not reveal overt changes in endogenous expression, subcellular localization, or enzymatic activity in the heterozygous carrier of the CTSB variant. The identification of the CTSB p.Gly284Val may support the hypothesis that the CTSB locus harbors variants with differing penetrance that can determine the disease risk.

Numerous studies have highlighted the role of the gastrointestinal system in Parkinson disease pathogenesis. It is likely triggered by proinflammatory markers produced by specific gut bacteria. This review’s aim is to identify gut bacterial biomarkers of Parkinson disease. A comprehensive search for original research papers on gut microbiota composition in Parkinson disease was conducted using the PubMed, Embase, and Scopus databases. Research papers on intestinal permeability, nasal and oral microbiomes, and interventional studies were excluded. The yielded results were categorized into four groups: Parkinson disease vs. healthy controls; disease severity; non-motor symptoms; and clinical phenotypes. This review was conducted in accordance with the PRISMA 2020 statement. A total of 51 studies met the eligibility criteria. In the Parkinson disease vs. healthy controls group, 22 bacteria were deemed potentially important. In the disease severity category, two bacteria were distinguished. In the non-motor symptoms and clinical phenotypes categories, no distinct pathogen was identified. The studies in this review report bacteria of varying taxonomic levels, which prevents the authors from reaching a clear conclusion. Future research should follow a unified methodology in order to identify potential biomarkers for Parkinson disease.

Parkinson’s disease (PD) is a progressive neurodegenerative disorder. It affects many organs. Lewy bodies—a histopathological “hallmark” of PD—are detected in about 75% of PD submandibular gland samples. We hypothesize that saliva can be a source of biomarkers of PD. The aim of the study was to evaluate and compare the salivary proteome of PD patients and healthy controls (HC). Salivary samples from 39 subjects (24 PD patients, mean age 61.6 ± 8.2; 15 HC, mean age 60.9 ± 6.7) were collected. Saliva was collected using RNA-Pro-Sal kits. Label-free LC-MS/MS mass spectrometry was performed to characterize the proteome of the saliva. IPA analysis of upstream inhibitors was performed. A total of 530 proteins and peptides were identified. We observed lower concentrations of S100-A16, ARP2/3, and VPS4B in PD group when compared to HC. We conclude that the salivary proteome composition of PD patients is different than that of healthy controls. We observed a lower concentration of proteins involved in inflammatory processes, exosome formation, and adipose tissue formation. The variability of expression of proteins between the two groups needs to be considered.