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Current Developments in Nutrition Jun 2024This article explores the potential therapeutic implications of phytochemicals on the gut-brain axis (GBA), which serves as a communication network between the central... (Review)
Review
This article explores the potential therapeutic implications of phytochemicals on the gut-brain axis (GBA), which serves as a communication network between the central nervous system and the enteric nervous system. Phytochemicals, which are compounds derived from plants, have been shown to interact with the gut microbiota, immune system, and neurotransmitter systems, thereby influencing brain function. Phytochemicals such as polyphenols, carotenoids, flavonoids, and terpenoids have been identified as having potential therapeutic implications for various neurological disorders. The GBA plays a critical role in the development and progression of various neurological disorders, including Parkinson's disease, multiple sclerosis, depression, anxiety, and autism spectrum disorders. Dysbiosis, or an imbalance in gut microbiota composition, has been associated with a range of neurological disorders, suggesting that modulating the gut microbiota may have potential therapeutic implications for these conditions. Although these findings are promising, further research is needed to elucidate the optimal use of phytochemicals in neurological disorder treatment, as well as their potential interactions with other medications. The literature review search was conducted using predefined search terms such as phytochemicals, gut-brain axis, neurodegenerative, and Parkinson in PubMed, Embase, and the Cochrane library.
PubMed: 38939650
DOI: 10.1016/j.cdnut.2024.103785 -
Parkinson's Disease 2024Postural instability and gait difficulties (PIGD) are a significant cause of falls, mobility loss, and lower quality of life in Parkinson's disease (PD). The connection...
BACKGROUND
Postural instability and gait difficulties (PIGD) are a significant cause of falls, mobility loss, and lower quality of life in Parkinson's disease (PD). The connection between PD progression and diminished strength in the lower limbs has been acknowledged. However, the identification of specific muscle groups linked to PIGD and non-PIGD motor features is still unknown.
OBJECTIVE
To explore the relationship between the strength of specific lower limb muscle groups, along with muscle mass, and their associations with PIGD, PIGD subtypes, and non-PIGD motor features in PD.
METHODS
95 PD participants underwent detailed motor and non-motor test batteries, including lower limb isometric strength testing and whole-body lean mass assessments. Correlation analysis and univariate and multivariate linear/logistic forward stepwise regression were performed to test associations between PIGD and non-PIGD motor features with normalized value (z-score) of lower limb muscle strength and measures of lean mass.
RESULTS
Multivariate regression analysis, adjusted for age, gender, and levodopa equivalent dose, revealed that hip abductor strength was significantly associated with overall PIGD motor severity ratings ( < 0.001), impaired balance ( < 0.001), and non-PIGD Parkinsonian motor features ( < 0.001). Conversely, hip extensor strength was significantly associated with falls, slow walking, and FoG motor features (=0.016; =0.003; =0.020, respectively).
CONCLUSION
We found that lower hip abductor strength was associated with PIGD and non-PIGD motor features. The association between non-PIGD motor features may suggest specific vulnerability of the hip abductors as part of a proposed brain-muscle loop hypothesis in PD. Moreover, lower hip extensor strength correlated with falls, slow walking, and FoG.
PubMed: 38939534
DOI: 10.1155/2024/5580870 -
Parkinson's Disease 2024Fatigue is a common and debilitating symptom affecting a significant proportion of individuals with Parkinson's disease (PD), often overshadowing even motor symptoms in... (Review)
Review
Fatigue is a common and debilitating symptom affecting a significant proportion of individuals with Parkinson's disease (PD), often overshadowing even motor symptoms in its impact on quality of life. The accurate definition and assessment of mental fatigue in PD is crucial for both clinical management and research, yet it remains a challenge due to the subjective nature of the symptom and the heterogeneity of assessment scales. This systematic review examined the existing measures of self-reported mental fatigue in PD by searching through PubMed, Embase, and Scopus databases using specific keywords from 2001 to 2024. Out of the 4182 articles found, 40 met the inclusion criteria, and 14 different scales were identified to measure self-reported fatigue in PD patients. However, most of these scales lack a consistent definition of fatigue, indicating a need for validated combinations of unidimensional and multidimensional scales to accurately assess mental fatigue in PD. The review found that it is best to use Fatigue Severity Inventory (FSI) and Multidimensional Fatigue Inventory (MdFI) to screen for severity of PD mental fatigue and Neuro-QoL Item Bank v1.0 (Neuro-QoL) to evaluate its impact on patients' lives. Furthermore, multidimensional scales Parkinson's Disease Questionnaire (PDQ) and Functional Assessment of Chronic Illness Therapy-Fatigue Scale (FACIT-F) are frequently coupled with Fatigue Severity Scale (FSS), Parkinson's Fatigue Scale (PFS), and/or Modified Fatigue Impact Scale (MFIS) due to their short length and holistic coverage of variables in patients' quality of life. Combining fatigue scales can be used for screening and scoring methods. The review also recommends validating fatigue scales translation and combining them with biomarkers to improve the accuracy and effectiveness of fatigue assessment in clinical practice. Future research should analyze correlations between fatigue scales, expand language types, and explore the link between fatigue scales and the pathophysiological basis of PD. Our findings underscore the need for a standardized approach to the measurement of fatigue in PD and set the stage for future research to consolidate assessment tools that can reliably guide treatment strategies and improve patient outcomes.
PubMed: 38939533
DOI: 10.1155/2024/9614163 -
Journal of Extracellular Biology Nov 2023Parkinsonian disorders, including Parkinson's disease (PD), multiple system atrophy (MSA), dementia with Lewy body (DLB), corticobasal syndrome (CBS) and progressive... (Review)
Review
Parkinsonian disorders, including Parkinson's disease (PD), multiple system atrophy (MSA), dementia with Lewy body (DLB), corticobasal syndrome (CBS) and progressive supranuclear palsy (PSP) are often misdiagnosed due to overlapping symptoms and the absence of precise biomarkers. Furthermore, there are no current methods to ascertain the progression and conversion of prodromal conditions such as REM behaviour disorder (RBD). Extracellular vesicles (EVs), containing a mixture of biomolecules, have emerged as potential sources for parkinsonian diagnostics. However, inconsistencies in previous studies have left their diagnostic potential unclear. We conducted a meta-analysis, following PRISMA guidelines, to assess the diagnostic accuracy of general EVs isolated from various bodily fluids, including cerebrospinal fluid (CSF), plasma, serum, urine or saliva, in differentiating patients with parkinsonian disorders from healthy controls (HCs). The meta-analysis included 21 studies encompassing 1285 patients with PD, 24 with MSA, 105 with DLB, 99 with PSP, 101 with RBD and 783 HCs. Further analyses were conducted only for patients with PD versus HCs, given the limited number for other comparisons. Using bivariate and hierarchal receiver operating characteristics (HSROC) models, the meta-analysis revealed moderate diagnostic accuracy in distinguishing patients with PD from HCs, with substantial heterogeneity and publication bias. The trim-and-fill method revealed at least two missing studies with null or low diagnostic accuracy. CSF-EVs showed better overall diagnostic accuracy, while plasma-EVs had the lowest performance. General EVs demonstrated higher diagnostic accuracy compared to CNS-originating EVs, which are more time-consuming, labour- and cost-intensive to isolate. In conclusion, while holding promise, utilizing biomarkers in general EVs for PD diagnosis remains unfeasible due to existing challenges. The focus should shift toward harmonizing the field through standardization, collaboration, and rigorous validation. Current efforts by the International Society For Extracellular Vesicles (ISEV) aim to enhance the accuracy and reproducibility of EV-related research through rigor and standardization, aiming to bridge the gap between theory and practical clinical application.
PubMed: 38939363
DOI: 10.1002/jex2.121 -
JACS Au Jun 2024The characterization of intrinsically disordered regions (IDRs) in membrane-associated proteins is of crucial importance to elucidate key biochemical processes,...
The characterization of intrinsically disordered regions (IDRs) in membrane-associated proteins is of crucial importance to elucidate key biochemical processes, including cellular signaling, drug targeting, or the role of post-translational modifications. These protein regions pose significant challenges to powerful analytical techniques of molecular structural investigations. We here applied magic angle spinning solid-state nuclear magnetic resonance to quantitatively probe the structural dynamics of IDRs of membrane-bound α-synuclein (αS), a disordered protein whose aggregation is associated with Parkinson's disease (PD). We focused on the mitochondrial binding of αS, an interaction that has functional and pathological relevance in neuronal cells and that is considered crucial for the underlying mechanisms of PD. Transverse and longitudinal N relaxation revealed that the dynamical properties of IDRs of αS bound to the outer mitochondrial membrane (OMM) are different from those of the cytosolic state, thus indicating that regions generally considered not to interact with the membrane are in fact affected by the spatial proximity with the lipid bilayer. Moreover, changes in the composition of OMM that are associated with lipid dyshomeostasis in PD were found to significantly perturb the topology and dynamics of IDRs in the membrane-bound state of αS. Taken together, our data underline the importance of characterizing IDRs in membrane proteins to achieve an accurate understanding of the role that these elusive protein regions play in numerous biochemical processes occurring on cellular surfaces.
PubMed: 38938811
DOI: 10.1021/jacsau.4c00323 -
Frontiers in Neurology 2024Recently, there has been increasing attention on the impact of acupuncture on the dysregulated neural circuits in different disease. This has led to new understandings... (Review)
Review
Recently, there has been increasing attention on the impact of acupuncture on the dysregulated neural circuits in different disease. This has led to new understandings of how acupuncture works. This review presents a comprehensive analysis of research that have examined the impact of acupuncture on abnormal neural circuits associated with pain, anxiety, Parkinson's disease, addiction disorders, cognitive problems, and gastrointestinal disorders. These studies have shown that acupuncture's therapeutic effects are mediated by specific brain areas and neurons involved in neural circuit mechanisms, emphasising its wide-ranging influence. The positive impacts of acupuncture can be ascribed to its ability to modify the functioning of neurocircuits in various physiological conditions. Nevertheless, contemporary studies on acupuncture neural circuits frequently overlook the comprehensive circuit mechanism including the periphery, central nervous system, and target organ. Additionally, the scope of diseases studied is restricted. Future study should focus on broadening the range of diseases studied and exploring the neural circuit mechanisms of these diseases in depth in order to enhance our understanding of acupuncture's neurobiological impacts.
PubMed: 38938783
DOI: 10.3389/fneur.2024.1399925 -
Innovations in Clinical Neuroscience 2024Well-known adverse events of antipsychotics are movement disorders, or extrapyramidal symptoms, such as drug-induced parkinsonism and tardive dyskinesia.
INTRODUCTION
Well-known adverse events of antipsychotics are movement disorders, or extrapyramidal symptoms, such as drug-induced parkinsonism and tardive dyskinesia.
OBJECTIVE
With new evidence suggesting a link between low high-density lipoprotein cholesterol (HDL-C) and risk of Parkinson's disease, this study sought to investigate if that link also translated to patients taking antipsychotics with low HDL-C and an increased risk for developing a movement disorder.
DESIGN
Adult patients (n=89) at an inpatient state psychiatric facility taking at least one antipsychotic with at least one HDL-C level were assessed for signs of a movement disorder through their history and physical, progress notes, and Abnormal Involuntary Movement Scale (AIMS) score.
RESULTS
There was no statistical significance when comparing a patient's movement disorder, AIMS scores, and HDL-C levels to suggest that the HDL-C level influenced a patient's movement disorder.
CONCLUSION
This study did not show a correlation between HDL-C levels and a patient's risk of developing a movement disorder while taking an antipsychotic.
PubMed: 38938537
DOI: No ID Found -
Frontiers in Human Neuroscience 2024Bradykinesia is an essential diagnostic criterion for Parkinson's disease (PD) but is frequently observed in many non-parkinsonian movement disorders, complicating...
INTRODUCTION
Bradykinesia is an essential diagnostic criterion for Parkinson's disease (PD) but is frequently observed in many non-parkinsonian movement disorders, complicating differential diagnosis, particularly in disorders featuring tremors. The presence of bradykinetic features in the subset of dystonic tremors (DT), either "pure" dystonic tremors or tremors associated with dystonia, remains currently unexplored. The aim of the current study was to evaluate upper limb bradykinesia in DT patients, comparing them with healthy controls (HC) and patients with PD by observing repetitive finger tapping (FT).
METHODS
The protocol consisted of two main parts. Initially, the kinematic recording of repetitive FT was performed using optical hand tracking system (Leap Motion Controller). The values of amplitude, amplitude decrement, frequency, frequency decrement, speed, acceleration and number of halts of FT were calculated. Subsequently, three independent movement disorder specialists from different movement disorders centres, blinded to the diagnosis, rated the presence of FT bradykinesia based on video recordings.
RESULTS
Thirty-six subjects participated in the study (12 DT, 12 HC and 12 early-stage PD). Kinematic analysis revealed no significant difference in the selected parameters of FT bradykinesia between DT patients and HC. In comparisons between DT and PD patients, PD patients exhibited bigger amplitude decrement and slower FT performance. In the blinded clinical assessment, bradykinesia was rated, on average, as being present in 41.6% of DT patients, 27.7% of HC, and 91.7% of PD patients. While overall inter-rater agreement was moderate, weak agreement was noted within the DT group.
DISCUSSION
Clinical ratings indicated signs of bradykinesia in almost half of DT patients. The objective kinematic analysis confirmed comparable parameters between DT and HC individuals, with more pronounced abnormalities in PD across various kinematic parameters. Interpretation of bradykinesia signs in tremor patients with DT should be approached cautiously and objective motion analysis might complement the diagnostic process and serve as a decision support system in the choice of clinical entities.
PubMed: 38938290
DOI: 10.3389/fnhum.2024.1395827 -
Psychiatry and Clinical Neurosciences Jun 2024
PubMed: 38938128
DOI: 10.1111/pcn.13705 -
Drug and Chemical Toxicology Jun 2024Parkinson's disease (PD) is a prevalent neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and...
Neuroprotective potential of solanesol against tramadol induced zebrafish model of Parkinson's disease: insights from neurobehavioral, molecular, and neurochemical evidence.
Parkinson's disease (PD) is a prevalent neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and subsequent depletion of dopamine in the striatum. Solanesol, an alcohol that acts as a precursor to coenzyme Q10, possesses potential applications in managing neurological disorders with antioxidant, anti-inflammatory, and neuromodulatory potential. In this study, a zebrafish model was employed to investigate the effects of solanesol in tramadol induced PD like symptoms. Zebrafish were administered tramadol injections (50 mg/kg) over a 20-day period. Solanesol was administered at doses of 25, 50, and 100 mg/kg, three hours prior to tramadol administration from day 11 to day 20. Behavioral tests assessing motor coordination were conducted on a weekly basis using open field and novel diving tank apparatus. On day 21, the zebrafish were euthanized, and brain tissues were examined for markers of oxidative stress, inflammation, and neurotransmitters level. Chronic tramadol treatment resulted in motor impairment, reduced antioxidant enzyme levels, enhanced release of proinflammatory cytokines in the striatum, and disrupted neurotransmitter balance. However, solanesol administration mitigated these effects and exhibited a neuroprotective effect against neurodegenerative alterations in the zebrafish model of PD. This was evident through improvements in behavior, modulation of biochemical markers, attenuation of neuroinflammation, restoration of neurotransmitters level, and enhancement of mitochondrial activity. The histopathological study also confirmed that solanesol dose dependently restored neuronal cell density which confirmed its neuroprotective potential. Further investigations are required to elucidate the underlying mechanisms of solanesol neuroprotective effects and evaluate its efficacy in human patients.
PubMed: 38938099
DOI: 10.1080/01480545.2024.2355542