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Biomedicine & Pharmacotherapy =... Jul 2024Central nervous system (CNS) disorders exhibit exceedingly intricate pathogenic mechanisms. Pragmatic and effective solutions remain elusive, significantly compromising... (Review)
Review
Central nervous system (CNS) disorders exhibit exceedingly intricate pathogenic mechanisms. Pragmatic and effective solutions remain elusive, significantly compromising human life and health. Activating transcription factor 4 (ATF4) participates in the regulation of multiple pathophysiological processes, including CNS disorders. Considering the widespread involvement of ATF4 in the pathological process of CNS disorders, the targeted regulation of ATF4 by plant-derived bioactive compounds (PDBCs) may become a viable strategy for the treatment of CNS disorders. However, the regulatory relationship between PDBCs and ATF4 remains incompletely understood. Here, we aimed to comprehensively review the studies on PDBCs targeting ATF4 to ameliorate CNS disorders, thereby offering novel directions and insights for the treatment of CNS disorders. A computerized search was conducted on PubMed, Embase, Web of Science, and Google Scholar databases to identify preclinical experiments related to PDBCs targeting ATF4 for the treatment of CNS disorders. The search timeframe was from the inception of the databases to December 2023. Two assessors conducted searches using the keywords "ATF4," "Central Nervous System," "Neurological," "Alzheimer's disease," "Parkinson's Disease," "Stroke," "Spinal Cord Injury," "Glioblastoma," "Traumatic Brain Injury," and "Spinal Cord Injury." Overall, 31 studies were included, encompassing assessments of 27 PDBCs. Combining results from in vivo and in vitro studies, we observed that these PDBCs, via ATF4 modulation, prevent the deposition of amyloid-like fibers such as Aβ, tau, and α-synuclein. They regulate ERS, reduce the release of inflammatory factors, restore mitochondrial membrane integrity to prevent oxidative stress, regulate synaptic plasticity, modulate autophagy, and engage anti-apoptotic mechanisms. Consequently, they exert neuroprotective effects in CNS disorders. Numerous PDBCs targeting ATF4 have shown potential in facilitating the restoration of CNS functionality, thereby presenting expansive prospects for the treatment of such disorders. However, future endeavors necessitate high-quality, large-scale, and comprehensive preclinical and clinical studies to further validate this therapeutic potential.
Topics: Activating Transcription Factor 4; Humans; Central Nervous System Diseases; Animals; Phytochemicals; Neuroprotective Agents
PubMed: 38795641
DOI: 10.1016/j.biopha.2024.116811 -
Life (Basel, Switzerland) May 2024Neurodegenerative diseases such as dementia and Parkinson's disease pose significant challenges to older adults globally. While pharmacological treatments remain... (Review)
Review
Neurodegenerative diseases such as dementia and Parkinson's disease pose significant challenges to older adults globally. While pharmacological treatments remain primary, increasing evidence supports the role of non-pharmacological strategies like physical activity in managing these conditions. This systematic review critically evaluates the effectiveness of Nursing based physical activity interventions in improving cognitive function, physical functioning, mobility, and overall quality of life among older adults with neurodegenerative diseases. We conducted a comprehensive search across PubMed, EMBASE, Web of Science, CENTRAL, and other relevant databases, focusing on randomized controlled trials and observational studies that examined the impact of structured physical activity. Our findings from nineteen studies involving 1673 participants indicate that interventions ranging from aerobic exercises, resistance training, to mind-body exercises like Tai Chi and yoga have beneficial effects. Specifically, physical activity was consistently found to enhance cognitive performance, increase mobility, and improve balance and daily living activities, contributing to a better quality of life. However, these benefits vary depending on the type, intensity, and duration of the activity performed. Despite promising results, limitations such as small sample sizes, study heterogeneity, and short-term follow-up periods call for more robust, long-term studies to solidify these findings. This review underscores the potential of tailored physical activity programs as adjunctive therapy in the comprehensive management of neurodegenerative diseases among the elderly population.
PubMed: 38792618
DOI: 10.3390/life14050597 -
International Journal of Molecular... May 2024Parkinson's disease (PD) is the second most common neurodegenerative disease worldwide. Given its prevalence, reliable biomarkers for early diagnosis are required.... (Meta-Analysis)
Meta-Analysis Review
Parkinson's disease (PD) is the second most common neurodegenerative disease worldwide. Given its prevalence, reliable biomarkers for early diagnosis are required. Exosomal proteins within extracellular nanovesicles are promising candidates for diagnostic, screening, prognostic, and disease monitoring purposes in neurological diseases such as PD. This review aims to evaluate the potential of extracellular vesicle proteins or miRNAs as biomarkers for PD. A comprehensive literature search until January 2024 was conducted across multiple databases, including PubMed, EMBASE, Web of Science, and Cochrane Library, to identify relevant studies reporting exosome biomarkers in blood samples from PD patients. Out of 417 articles screened, 47 studies were selected for analysis. Among exosomal protein biomarkers, α-synuclein, tau, Amyloid β 1-42, and C-X-C motif chemokine ligand 12 (CXCL12) were identified as significant markers for PD. Concerning miRNA biomarkers, miRNA-24, miR-23b-3p, miR-195-3p, miR-29c, and mir-331-5p are promising across studies. α-synuclein exhibited increased levels in PD patients compared to control groups in twenty-one studies, while a decrease was observed in three studies. Our meta-analysis revealed a significant difference in total exosomal α-synuclein levels between PD patients and healthy controls (standardized mean difference [SMD] = 1.369, 95% confidence interval [CI] = 0.893 to 1.846, < 0.001), although these results are limited by data availability. Furthermore, α-synuclein levels significantly differ between PD patients and healthy controls (SMD = 1.471, 95% CI = 0.941 to 2.002, < 0.001). In conclusion, certain exosomal proteins and multiple miRNAs could serve as potential biomarkers for diagnosis, prognosis prediction, and assessment of disease progression in PD.
Topics: Humans; Parkinson Disease; Exosomes; Biomarkers; MicroRNAs; alpha-Synuclein; Amyloid beta-Peptides
PubMed: 38791346
DOI: 10.3390/ijms25105307 -
International Journal of Molecular... May 2024The gene encodes an orphan transcription factor of the steroid-thyroid hormone-retinoid receptor superfamily. This review focuses on the clinical findings associated... (Review)
Review
The gene encodes an orphan transcription factor of the steroid-thyroid hormone-retinoid receptor superfamily. This review focuses on the clinical findings associated with the pathogenic variants so far reported, including three unreported cases. Also, its role in neurodegenerative diseases, such as Parkinson's or Alzheimer's disease, is examined, as well as a brief exploration on recent proposals to develop novel therapies for these neurological diseases based on small molecules that could modulate transcriptional activity. The main characteristic shared by all patients is mild to severe developmental delay/intellectual disability. Moderate to severe disorder of the expressive and receptive language is present in at least 42%, while neuro-psychiatric issues were reported in 53% of patients. Movement disorders, including dystonia, chorea or ataxia, are described in 37% patients, although probably underestimated because of its frequent onset in late adolescence-young adulthood. Finally, epilepsy was surprisingly present in 42% of patients, being drug-resistant in three of them. The age at onset varied widely, from five months to twenty-six years, as did the classification of epilepsy, which ranged from focal epilepsy to infantile spasms or Lennox-Gastaut syndrome. Accordingly, we propose that should be considered as a first-tier target gene for the genetic diagnosis of developmental and epileptic encephalopathy.
Topics: Humans; Epilepsy; Nuclear Receptor Subfamily 4, Group A, Member 2; Developmental Disabilities; Intellectual Disability
PubMed: 38791237
DOI: 10.3390/ijms25105198 -
Brain Sciences May 2024People with Parkinson's disease (pwPD) present alterations of spatiotemporal gait parameters that impact walking ability. While preliminary studies suggested that... (Review)
Review
BACKGROUND
People with Parkinson's disease (pwPD) present alterations of spatiotemporal gait parameters that impact walking ability. While preliminary studies suggested that dual-task gait training improves spatiotemporal gait parameters, it remains unclear whether dual-task gait training specifically improves dual-task gait performance compared to single-task gait training. The aim of this review is to assess the effect of dual-task training relative to single-task gait training on specific gait parameters during dual-task tests in pwPD.
METHODS
We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs), searching three electronic databases. Two reviewers independently selected RCTs, extracted data, and applied the Cochrane risk-of-bias tool for randomized trials (Version 2) and the GRADE framework for assessing the certainty of evidence. The primary outcomes were dual-task gait speed, stride length, and cadence. Secondary outcomes included dual-task costs on gait speed, balance confidence, and quality of life.
RESULTS
We included 14 RCTs (548 patients). Meta-analyses showed effects favoring dual-task training over single-task training in improving dual-task gait speed (standardized mean difference [SMD] = 0.48, 95% confidence interval [CI] = 0.20-0.77; 11 studies; low certainty evidence), stride length (mean difference [MD] = 0.09 m, 95% CI = 0.04-0.14; 4 studies; very low certainty evidence), and cadence (MD = 5.45 steps/min, 95% CI = 3.59-7.31; 5 studies; very low certainty evidence). We also found a significant effect of dual-task training over single-task training on dual-task cost and quality of life, but not on balance confidence.
CONCLUSIONS
Our findings support the use of dual-task training relative to single-task training to improve dual-task spatiotemporal gait parameters in pwPD. Further studies are encouraged to better define the features of dual-task training and the clinical characteristics of pwPD to identify better responders.
PubMed: 38790495
DOI: 10.3390/brainsci14050517 -
Bioengineering (Basel, Switzerland) May 2024Recognizing the growing interests and benefits of technology-assisted interactive telerehabilitation in various populations, the aim of this review is to systematically... (Review)
Review
A Systematic Review of the Effects of Interactive Telerehabilitation with Remote Monitoring and Guidance on Balance and Gait Performance in Older Adults and Individuals with Neurological Conditions.
Recognizing the growing interests and benefits of technology-assisted interactive telerehabilitation in various populations, the aim of this review is to systematically review the effects of interactive telerehabilitation with remote monitoring and guidance for improving balance and gait performance in older adults and individuals with neurological conditions. The study protocol for this systematic review was registered with the international prospective register of systematic reviews (PROSPERO) with the unique identifier CRD42024509646. Studies written in English published from January 2014 to February 2024 in Web of Science, Pubmed, Scopus, and Google Scholar were examined. Of the 247 identified, 17 were selected after initial and eligibility screening, and their methodological quality was assessed with the National Institutes of Health Quality Assessment Tool for Observational Cohort and Cross-sectional Studies. All 17 studies demonstrated balance and gait performance improvement in older adults and in individuals with stroke, Parkinson's disease, and multiple sclerosis following 4 or more weeks of interactive telerehabilitation via virtual reality, smartphone or tablet apps, or videoconferencing. The findings of this systematic review can inform the future design and implementation of interactive telerehabilitation technology and improve balance and gait training exercise regimens for older adults and individuals with neurological conditions.
PubMed: 38790328
DOI: 10.3390/bioengineering11050460 -
Toxins May 2024Axial postural abnormalities (APAs), characterized by their frequency, disabling nature, and resistance to pharmacological treatments, significantly impact Parkinson's... (Review)
Review
Axial postural abnormalities (APAs), characterized by their frequency, disabling nature, and resistance to pharmacological treatments, significantly impact Parkinson's disease and atypical Parkinsonism patients. Despite advancements in diagnosing, assessing, and understanding their pathophysiology, managing these complications remains a significant challenge. Often underestimated by healthcare professionals, these disturbances can exacerbate disability. This systematic review assesses botulinum toxin treatments' effectiveness, alone and with rehabilitation, in addressing APAs in Parkinson's disease, utilizing MEDLINE (PubMed), Web of Science, and SCOPUS databases for source material. Of the 1087 records retrieved, 16 met the selection criteria. Most research has focused on botulinum toxin (BoNT) as the primary treatment for camptocormia and Pisa syndrome, utilizing mostly observational methods. Despite dose and injection site variations, a common strategy was using electromyography-guided injections, occasionally enhanced with ultrasound. Patients with Pisa syndrome notably saw consistent improvements in APAs and pain. However, studies on the combined effects of botulinum toxin and rehabilitation are limited, and antecollis is significantly under-researched. These findings recommend precise BoNT injections into hyperactive muscles in well-selected patients by skilled clinicians, avoiding compensatory muscles, and underscore the necessity of early rehabilitation. Rehabilitation is crucial in a multidisciplinary approach to managing APAs, highlighting the importance of a multidisciplinary team of experts.
Topics: Humans; Parkinson Disease; Botulinum Toxins; Neuromuscular Agents; Spinal Curvatures; Posture
PubMed: 38787080
DOI: 10.3390/toxins16050228 -
European Journal of Investigation in... May 2024Parkinson's disease (PD) is a neurological disorder caused by the loss of dopamine-producing cells in the substantia nigra and characterized by motor and non-motor... (Review)
Review
Parkinson's disease (PD) is a neurological disorder caused by the loss of dopamine-producing cells in the substantia nigra and characterized by motor and non-motor symptoms. Boxing is a type of complementary therapy to improve symptoms in PD. The purpose of the present study was to examine the effect of boxing training on the functionality and quality of life of patients with PD. The literature search was performed on PubMed, Scopus, PEDro, Cochrane Library, and Google Scholar search engines. The PEDro scale was used to assess the methodological quality of the studies. This systematic review included three studies that examined disease severity, mobility, physical activity, balance, and quality of life. According to the PEDro scale criteria, the three articles included were of high methodological quality. Statistically significant improvements after the implementation of boxing training was shown for balance and quality of life in contrast to the other variables. Boxing training intervention programs had a positive effect on balance and quality of life in patients with PD; however, the results are conflicting regarding certain functionality variables. Therefore, it is necessary to conduct further research to examine the effectiveness of boxing training on the functionality and quality of life of patients with Parkinson's disease.
PubMed: 38785583
DOI: 10.3390/ejihpe14050085 -
Current Issues in Molecular Biology Apr 2024Gut microbiome-targeted interventions such as fecal transplant, prebiotics, probiotics, synbiotics, and antibiotic gut depletion are speculated to be of potential use in... (Review)
Review
Gut microbiome-targeted interventions such as fecal transplant, prebiotics, probiotics, synbiotics, and antibiotic gut depletion are speculated to be of potential use in delaying the onset and progression of Parkinson's disease by rebalancing the gut microbiome in the context of the gut-brain axis. Our study aims to organize recent findings regarding these interventions in Parkinson's disease animal models to identify how they affect neuroinflammation and motor outcomes. A systematic literature search was applied in PubMed, Web of Science, Embase, and SCOPUS for gut microbiome-targeted non-dietary interventions. Studies that investigated gut-targeted interventions by using in vivo murine PD models to follow dopaminergic cell loss, motor tests, and neuroinflammatory markers as outcomes were considered to be eligible. A total of 1335 studies were identified in the databases, out of which 29 were found to be eligible. A narrative systematization of the resulting data was performed, and the effect direction for the outcomes was represented. Quality assessment using the SYRCLE risk of bias tool was also performed. Out of the 29 eligible studies, we found that a significant majority report that the intervention reduced the dopaminergic cell loss (82.76%, 95% CI [64.23%, 94.15%]) produced by the induction of the disease model. Also, most studies reported a reduction in microglial (87.5%, 95% CI [61.65%, 98.45%]) and astrocytic activation (84,62%, 95% CI [54.55%, 98.08%]) caused by the induction of the disease model. These results were also mirrored in the majority (96.4% 95% CI [81.65%, 99.91%]) of the studies reporting an increase in performance in behavioral motor tests. A significant limitation of the study was that insufficient information was found in the studies to assess specific causes of the risk of bias. These results show that non-dietary gut microbiome-targeted interventions can improve neuroinflammatory and motor outcomes in acute Parkinson's disease animal models. Further studies are needed to clarify if these benefits transfer to the long-term pathogenesis of the disease, which is not yet fully understood. The study had no funding source, and the protocol was registered in the PROSPERO database with the ID number CRD42023461495.
PubMed: 38785512
DOI: 10.3390/cimb46050244 -
Epilepsy & Behavior Reports 2024Exercise interventions in epilepsy have been shown to improve seizure frequency, physical capacity, quality of life, mood, and cognitive functioning. However, the... (Review)
Review
Exercise interventions in epilepsy have been shown to improve seizure frequency, physical capacity, quality of life, mood, and cognitive functioning. However, the effectiveness of exercise in improving sleep in epilepsy is less clear. The purpose of this report is to identify the published literature regarding exercise interventions in people with epilepsy to determine 1) what proportion of published clinical trials assess sleep as an outcome, and 2) what benefits of exercise interventions on sleep have been observed. We searched the PubMed, PsycINFO, and SCOPUS electronic databases using the search terms "epilepsy AND [exercise OR physical activity]" and identified 23 articles reporting on 18 unique clinical trials. Nine studies were conducted in adults, five in children, and four in adults and children with active seizures, controlled seizures, or both. Exercise modalities included aerobic exercise, strength training, walking, and yoga, among others, and some also included educational and motivational components. Exercise effects on sleep were tested in four studies, two of which only included indirect measures of sleep- and rest-related fatigue, with mixed results. Of the two reports assessing sleep directly, one reported marginal non-significant improvements in subjective sleep quality and no improvements in objective sleep quality in children after twelve weeks of walking, and the other reported no benefits in subjective sleep quality after twelve weeks of combined aerobic, strength, and flexibility training in adults. Given the health benefits of sleep and detrimental effects of sleep deprivation in epilepsy, epilepsy researchers need to assess the effects of exercise interventions on sleep.
PubMed: 38779424
DOI: 10.1016/j.ebr.2024.100675