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Journal of Cellular and Molecular... Jun 2024Parkinson disease (PD) is one of the most common neurodegenerative diseases of the brain. Of note, brain renin-angiotensin system (RAS) is intricate in the PD... (Review)
Review
Parkinson disease (PD) is one of the most common neurodegenerative diseases of the brain. Of note, brain renin-angiotensin system (RAS) is intricate in the PD neuropathology through modulation of oxidative stress, mitochondrial dysfunction and neuroinflammation. Therefore, modulation of brain RAS by angiotensin receptor blockers (ARBs) and angiotensin-converting enzyme inhibitors (ACEIs) may be effective in reducing the risk and PD neuropathology. It has been shown that all components including the peptides and enzymes of the RAS are present in the different brain areas. Brain RAS plays a critical role in the regulation of memory and cognitive function, and in the controlling of central blood pressure. However, exaggerated brain RAS is implicated in the pathogenesis of different neurodegenerative diseases including PD. Two well-known pathways of brain RAS are recognized including; the classical pathway which is mainly mediated by AngII/AT1R has detrimental effects. Conversely, the non-classical pathway which is mostly mediated by ACE2/Ang1-7/MASR and AngII/AT2R has beneficial effects against PD neuropathology. Exaggerated brain RAS affects the viability of dopaminergic neurons. However, the fundamental mechanism of brain RAS in PD neuropathology was not fully elucidated. Consequently, the purpose of this review is to disclose the mechanistic role of RAS in in the pathogenesis of PD. In addition, we try to revise how the ACEIs and ARBs can be developed for therapeutics in PD.
Topics: Renin-Angiotensin System; Humans; Parkinson Disease; Brain; Animals; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors
PubMed: 38899551
DOI: 10.1111/jcmm.18495 -
World Journal of Clinical Cases Jun 2024Patients with Parkinson's disease (PD) often experience depression, and some may require magnetic resonance imaging (MRI) for diagnosis, which can lead to MRI failure... (Clinical Trial)
Clinical Trial
BACKGROUND
Patients with Parkinson's disease (PD) often experience depression, and some may require magnetic resonance imaging (MRI) for diagnosis, which can lead to MRI failure due to claustrophobia.
AIM
To explore the value of psychological interventions in successfully completing functional MRI scans of the brain for PD-related depression.
METHODS
Ninety-six patients with PD were randomly divided into two groups. The control group (47 patients) received general care, and the experimental group (49 patients) received general care combined with psychological care. The Unified Parkinson's Disease Assessment Scale (UPDRS), Hamilton Depression Scale (HAMD), and Geriatric Depression Scale (GDS)-15 scores, heart rate, systolic blood pressure, and MRI-Anxiety Questionnaire (MRI-AQ) scores before and after the scan were recorded. The completion rate of magnetic resonance (MR) scanning, scanning duration, and image quality scores were recorded.
RESULTS
Before scanning, no statistically significant difference was observed between the two groups in terms of heart rate, systolic blood pressure, and UPDRS, HAMD, GDS-15, and MRI-AQ scores. After scanning, systolic blood pressure, MRI-AQ score, and scan time in the experimental group were significantly lower than those in the control group, whereas the scan completion rate and image quality score were significantly higher than those in the control group.
CONCLUSION
Psychological nursing interventions are helpful in alleviating PD-related depression and assessing MR depression scores and may be helpful in the successful completion of functional MRI scans of the patient's brain.
PubMed: 38898827
DOI: 10.12998/wjcc.v12.i17.3086 -
Biomolecules & Therapeutics Jul 2024The human gastrointestinal (GI) tract houses a diverse microbial community, known as the gut microbiome comprising bacteria, viruses, fungi, and protozoa. The gut... (Review)
Review
The human gastrointestinal (GI) tract houses a diverse microbial community, known as the gut microbiome comprising bacteria, viruses, fungi, and protozoa. The gut microbiome plays a crucial role in maintaining the body's equilibrium and has recently been discovered to influence the functioning of the central nervous system (CNS). The communication between the nervous system and the GI tract occurs through a two-way network called the gut-brain axis. The nervous system and the GI tract can modulate each other through activated neuronal cells, the immune system, and metabolites produced by the gut microbiome. Extensive research both in preclinical and clinical realms, has highlighted the complex relationship between the gut and diseases associated with the CNS, such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. This review aims to delineate receptor and target enzymes linked with gut microbiota metabolites and explore their specific roles within the brain, particularly their impact on CNS-related diseases.
PubMed: 38898687
DOI: 10.4062/biomolther.2024.009 -
Journal of Extracellular Vesicles Jun 2024Extracellular vesicles (EVs) carry disease-specific molecular profiles, demonstrating massive potential in biomarker discovery. In this study, we developed an integrated...
Extracellular vesicles (EVs) carry disease-specific molecular profiles, demonstrating massive potential in biomarker discovery. In this study, we developed an integrated biochip platform, termed EVID-biochip (EVs identification and detection biochip), which integrates in situ electrochemical protein detection with on-chip antifouling-immunomagnetic beads modified with CD81 antibodies and zwitterion molecules, enabling efficient isolation and detection of neuronal EVs. The capability of the EVID-biochip to isolate common EVs and detect neuronal EVs associated with Parkinson's disease in human serum is successfully demonstrated, using the transmembrane protein L1-cell adhesion molecule (L1CAM) as a target biomarker. The EVID-biochip exhibited high efficiency and specificity for the detection of L1CAM with a sensitivity of 1 pg/mL. Based on the validation of 76 human serum samples, for the first time, this study discovered that the level of L1CAM/neuronal EV particles in serum could serve as a reliable indicator to distinguish Parkinson's disease from control groups with AUC = 0.973. EVID-biochip represents a reliable and rapid liquid biopsy platform for the analysis of complex biofluids offering EVs isolation and detection in a single chip, requiring a small sample volume (300 µL) and an assay time of 1.5 h. This approach has the potential to advance the diagnosis and biomarker discovery of various neurological disorders and other diseases.
Topics: Parkinson Disease; Humans; Extracellular Vesicles; Neural Cell Adhesion Molecule L1; Biomarkers; Male; Female; Liquid Biopsy; Aged; Middle Aged
PubMed: 38898558
DOI: 10.1002/jev2.12467 -
Translational Neurodegeneration Jun 2024The central nervous system (CNS) is integrated by glial and neuronal cells, and both release extracellular vesicles (EVs) that participate in CNS homeostasis. EVs could... (Review)
Review
The central nervous system (CNS) is integrated by glial and neuronal cells, and both release extracellular vesicles (EVs) that participate in CNS homeostasis. EVs could be one of the best candidates to operate as nanosized biological platforms for analysing multidimensional bioactive cargos, which are protected during systemic circulation of EVs. Having a window into the molecular level processes that are happening in the CNS could open a new avenue in CNS research. This raises a particular point of interest: can CNS-derived EVs in blood serve as circulating biomarkers that reflect the pathological status of neurological diseases? L1 cell adhesion molecule (L1CAM) is a widely reported biomarker to identify CNS-derived EVs in peripheral blood. However, it has been demonstrated that L1CAM is also expressed outside the CNS. Given that principal data related to neurodegenerative diseases, such as multiple sclerosis, amyotrophic lateral sclerosis, Parkinson's disease and Alzheimer's disease were obtained using L1CAM-positive EVs, efforts to overcome present challenges related to its specificity are required. In this sense, other surface biomarkers for CNS-derived EVs, such as glutamate aspartate transporter (GLAST) and myelin oligodendrocyte glycoprotein (MOG), among others, have started to be used. Establishing a panel of EV biomarkers to analyse CNS-derived EVs in blood could increase the specificity and sensitivity necessary for these types of studies. This review covers the main evidence related to CNS-derived EVs in cerebrospinal fluid and blood samples of patients with neurological diseases, focusing on the reported biomarkers and the technical possibilities for their isolation. EVs are emerging as a mirror of brain physiopathology, reflecting both localized and systemic changes. Therefore, when the technical hindrances for EV research and clinical applications are overcome, novel disease-specific panels of EV biomarkers would be discovered to facilitate transformation from traditional medicine to personalized medicine.
Topics: Humans; Extracellular Vesicles; Biomarkers; Central Nervous System; Neurodegenerative Diseases; Animals
PubMed: 38898538
DOI: 10.1186/s40035-024-00418-9 -
International Journal For Equity in... Jun 2024Alzheimer's disease and related dementias (ADRD) and Parkinson's disease (PD), pose growing global health challenges. Socio-demographic and economic development acts...
BACKGROUND
Alzheimer's disease and related dementias (ADRD) and Parkinson's disease (PD), pose growing global health challenges. Socio-demographic and economic development acts paradoxically, complicating the process that determines how governments worldwide designate policies and allocate resources for healthcare.
METHODS
We extracted data on ADRD and PD in 204 countries from the Global Burden of Disease 2019 database. Health disparities were estimated using the slope index of inequality (SII), and concentration index (CIX) based on the socio-demographic index. Estimated annual percentage changes (EAPCs) were employed to evaluate temporal trends.
RESULTS
Globally, the SII increased from 255.4 [95% confidence interval (CI), 215.2 to 295.5)] in 1990 to 559.3 (95% CI, 497.2 to 621.3) in 2019 for ADRD, and grew from 66.0 (95% CI, 54.9 to 77.2) in 1990 to 132.5 (95% CI, 118.1 to 147.0) in 2019 for PD; CIX rose from 33.7 (95% CI, 25.8 to 41.6) in 1990 to 36.9 (95% CI, 27.8 to 46.1) in 2019 for ADRD, and expanded from 22.2 (95% CI, 21.3 to 23.0) in 1990 to 29.0 (95% CI, 27.8 to 30.3) in 2019 for PD. Age-standardized disability-adjusted life years displayed considerable upward trends for ADRD [EAPC = 0.43 (95% CI, 0.27 to 0.59)] and PD [0.34 (95% CI, 0.29 to 0.38)].
CONCLUSIONS
Globally, the burden of ADRD and PD continues to increase with growing health disparities. Variations in health inequalities and the impact of socioeconomic development on disease trends underscored the need for targeted policies and strategies, with heightened awareness, preventive measures, and active management of risk factors.
Topics: Humans; Alzheimer Disease; Parkinson Disease; Global Health; Female; Male; Aged; Health Status Disparities; Socioeconomic Factors; Global Burden of Disease; Middle Aged; Health Inequities
PubMed: 38898437
DOI: 10.1186/s12939-024-02212-5 -
Scientific Reports Jun 2024Oropharyngeal dysphagia, or difficulty initiating swallowing, is a frequent problem in people with Parkinson's disease (PD) and can lead to aspiration pneumonia. The...
Oropharyngeal dysphagia, or difficulty initiating swallowing, is a frequent problem in people with Parkinson's disease (PD) and can lead to aspiration pneumonia. The efficacy of pharmacological options is limited. Postural strategies, such as a chin-down manoeuvre when drinking, have had some degree of success but may be difficult for people who have other limitations such as dementia or neck rigidity, to reproduce consistently. Using a user-centred design approach and a multidisciplinary team, we developed and tested an anti-choking mug for people with PD that helps angle the head in the optimum position for drinking. The design reflected anthropometric and ergonomic aspects of user needs with features including regulation of water flow rate and sip volume, an inner slope, a thickened handle and a wide base, which promoted a chin-down posture when used. Prototype testing using digital technology to compare neck flexion angles (the primary outcome), plus clinical outcomes assessed using standard tools (Swallowing Clinical Assessment Score in Parkinson's Disease (SCAS-PD) and Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts II and III), found significant improvements in a range of parameters related to efficient swallowing and safe drinking when using the anti-choking mug versus a sham mug.
Topics: Parkinson Disease; Humans; Male; Female; Deglutition Disorders; Aged; User-Centered Design; Deglutition; Middle Aged; Airway Obstruction; Posture
PubMed: 38898235
DOI: 10.1038/s41598-024-65071-8 -
NPJ Parkinson's Disease Jun 2024Increasing evidence suggests that the cerebellum may have a role in the pathophysiology of Parkinson's disease (PD). Hence, the scope of this study was to investigate...
Increasing evidence suggests that the cerebellum may have a role in the pathophysiology of Parkinson's disease (PD). Hence, the scope of this study was to investigate whether there are structural and functional alterations of the cerebellum and whether they correlate with motor and non-motor symptoms in early PD patients. Seventy-six patients with early PD and thirty-one age and sex-matched healthy subjects (HS) were enrolled and underwent a 3 T magnetic resonance imaging (MRI) protocol. The following MRI analyses were performed: (1) volumes of 5 cerebellar regions of interest (sensorimotor and cognitive cerebellum, dentate, interposed, and fastigial nuclei); (2) microstructural integrity of the cerebellar white matter connections (inferior, middle, and superior cerebellar peduncles); (3) functional connectivity at rest of the 5 regions of interest already described in point 1 with the rest of brain. Compared to controls, early PD patients showed a significant decrease in gray matter volume of the dentate, interposed and fastigial nuclei, bilaterally. They also showed abnormal, bilateral white matter microstructural integrity in all 3 cerebellar peduncles. Functional connectivity of the 5 cerebellar regions of interest with several areas in the midbrain, basal ganglia and cerebral cortex was altered. Finally, there was a positive correlation between abnormal functional connectivity of the fastigial nucleus with the volume of the nucleus itself and a negative correlation with axial symptoms severity. Our results showed that structural and functional alterations of the cerebellum are present in PD patients and these changes contribute to the pathophysiology of PD in the early phase.
PubMed: 38898032
DOI: 10.1038/s41531-024-00727-w -
Nature Communications Jun 2024Disrupted glucose metabolism and protein misfolding are key characteristics of age-related neurodegenerative disorders including Parkinson's disease, however their...
Disrupted glucose metabolism and protein misfolding are key characteristics of age-related neurodegenerative disorders including Parkinson's disease, however their mechanistic linkage is largely unexplored. The hexosamine biosynthetic pathway utilizes glucose and uridine-5'-triphosphate to generate N-linked glycans required for protein folding in the endoplasmic reticulum. Here we find that Parkinson's patient midbrain cultures accumulate glucose and uridine-5'-triphosphate, while N-glycan synthesis rates are reduced. Impaired glucose flux occurred by selective reduction of the rate-limiting enzyme, GFPT2, through disrupted signaling between the unfolded protein response and the hexosamine pathway. Failure of the unfolded protein response and reduced N-glycosylation caused immature lysosomal hydrolases to misfold and accumulate, while accelerating glucose flux through the hexosamine pathway rescued hydrolase function and reduced pathological α-synuclein. Our data indicate that the hexosamine pathway integrates glucose metabolism with lysosomal activity, and its failure in Parkinson's disease occurs by uncoupling of the unfolded protein response-hexosamine pathway axis. These findings offer new methods to restore proteostasis by hexosamine pathway enhancement.
Topics: Humans; Hexosamines; Lysosomes; Parkinson Disease; Unfolded Protein Response; Neurons; Induced Pluripotent Stem Cells; Mesencephalon; Glucose; Biosynthetic Pathways; Glycosylation; alpha-Synuclein; Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing)
PubMed: 38897986
DOI: 10.1038/s41467-024-49256-3 -
Journal of Physiotherapy Jun 2024In people with Parkinson's disease, what is the effect of adding external cueing (ie, visual, auditory or somatosensorial cueing) to walking training compared with...
QUESTIONS
In people with Parkinson's disease, what is the effect of adding external cueing (ie, visual, auditory or somatosensorial cueing) to walking training compared with walking training alone in terms of walking, mobility, balance, fear of falling and freezing? Are any benefits carried over to participation or maintained beyond the intervention period?
DESIGN
Systematic review of randomised trials with meta-analysis.
PARTICIPANTS
Ambulatory adults with Parkinson's disease.
INTERVENTION
Walking training with external cueing compared with walking training without external cueing.
OUTCOME MEASURES
Walking (ie, speed, stride length and cadence), mobility, balance, fear of falling, freezing and participation.
RESULTS
Ten trials involving a total of 309 participants were included. The mean PEDro score of the included trials was 5 (range 4 to 8). Walking training with auditory cueing improved walking speed by 0.09 m/s (95% CI 0.02 to 0.15) more than walking training alone. Although the best estimate was that auditory cueing may also improve stride length by 5 cm, this estimate was imprecise (95% CI -2 to 11). The addition of visual cueing to walking training did not improve walking speed or stride length. Results regarding cadence, mobility, balance, fear of falling, and freezing and maintenance of benefits beyond the intervention period remain uncertain.
CONCLUSION
This systematic review provided low-quality evidence that walking training with auditory cueing is more effective than walking training alone for improving walking speed in Parkinson's disease. Cueing is an inexpensive and easy to implement intervention, so the mean estimate might be considered clinically worthwhile, although the confidence interval spans clinically trivial and worthwhile effects.
REGISTRATION
PROSPERO CRD42021255065.
PubMed: 38897907
DOI: 10.1016/j.jphys.2024.06.004