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Journal of Ethnopharmacology Oct 2024Ganoderma lucidum, a renowned tonic traditional Chinese medicine, is widely recognized for the exceptional activity in soothing nerves and nourishing the brain. It has...
ETHNOPHARMACOLOGICAL RELEVANCE
Ganoderma lucidum, a renowned tonic traditional Chinese medicine, is widely recognized for the exceptional activity in soothing nerves and nourishing the brain. It has been extensively employed to alleviate various neurological disorders, notably Parkinson's disease (PD).
AIM OF THE STUDY
To appraise the antiparkinsonian effect of GAA, the main bioactive constituent of G. lucidum, and clarify the molecular mechanism through the perspective of ferritinophagy-mediated dopaminergic neuron ferroptosis.
MATERIALS AND METHODS
PD mouse and cell models were established using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 1-methyl-4-phenylpyridinium (MPP), respectively. Cell viability, behavioral tests and immunofluorescence analysis were performed to evaluate the neurotoxicity, motor dysfunction and dopaminergic loss, respectively. Biochemical assay kits were used to determine the levels of iron, lipid reactive oxygen species (ROS), malondialdehyde (MDA), total ROS and glutathione (GSH). Western blot and immunofluorescence were applied to detect the expressions of nuclear receptor co-activator 4 (NCOA4), ferritin heavy chain 1 (FTH1), p62 and LC3B. Additionally, NCOA4-overexpressing plasmid vector was constructed to verify the inhibitory effect of GAA on the neurotoxicity and ferroptosis-related parameters in PD models.
RESULTS
GAA significantly mitigated MPP/MPTP-induced neurotoxicity, motor dysfunction and dopaminergic neuron loss (p<0.01 or p<0.05). In contrast to MPP/MPTP treatment, GAA treatment decreased the levels of iron, MDA, lipid and total ROS, while increasing the GSH level. GAA also reduced the levels of NCOA4 and LC3B, and enhanced the expressions of FTH1 and p62 in PD models (p<0.01 or p<0.05). However, the protective effect of GAA against the neurotoxicity, NCOA4-mediated ferritinophagy and ferroptosis in PD model was abolished by the overexpression of NCOA4 (p<0.01).
CONCLUSION
GAA exerted a protective effect on PD, and this effect was achieved by suppressing dopaminergic neuron ferroptosis through the inhibition of NCOA4-mediated ferritinophagy.
Topics: Animals; Ferroptosis; Dopaminergic Neurons; Nuclear Receptor Coactivators; Mice; Mice, Inbred C57BL; Male; Ferritins; Neuroprotective Agents; Autophagy; Antiparkinson Agents; Parkinsonian Disorders; Parkinson Disease; Disease Models, Animal
PubMed: 38763373
DOI: 10.1016/j.jep.2024.118363 -
Sleep Medicine Jul 2024Dopamine agonists (DAs) constitute the standard therapeutic scheme for restless leg syndrome (RLS) because they have been proven to be effective. However, DAs may change... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Dopamine agonists (DAs) constitute the standard therapeutic scheme for restless leg syndrome (RLS) because they have been proven to be effective. However, DAs may change sleep parameters, thus having adverse effects on patient condition. This meta-analysis clarified the effects of DAs used in RLS treatment on the sleep architecture.
METHODS
PubMed, Embase, and Cochrane Central databases were searched for randomized control trials (RCT) (up to October 2023) that discussed the effects of DAs on sleep architecture in patients with RLS. A meta-analysis employing a random-effects model was conducted. The patients were divided into subgroups according to individual DAs and treatment duration (1 day or ≥4 weeks).
RESULTS
Thirteen eligible randomized placebo-controlled trials were included in the assessment. The effects of three DAs (i.e., pramipexole, ropinirole, and rotigotine) on rapid eye movement (REM) sleep, slow-wave sleep (SWS), and sleep efficiency (SE) were analyzed. Overall, pramipexole significantly improved SE but decreased the percentage of REM sleep among treated patients. Ropinirole also enhanced SE compared with the placebo group. Rotigotine did not affect SE and REM sleep. Subgroup analysis found that pramipexole used for 1 day and ≥4 weeks significantly diminished the percentage of REM sleep. Ropinirole used for 1 day showed similar REM sleep patterns. Finally, none of the three DAs affected SWS.
CONCLUSIONS
This meta-analysis demonstrated that DAs significantly affect sleep parameters.
Topics: Restless Legs Syndrome; Humans; Dopamine Agonists; Pramipexole; Randomized Controlled Trials as Topic; Tetrahydronaphthalenes; Sleep, REM; Indoles; Thiophenes
PubMed: 38761607
DOI: 10.1016/j.sleep.2024.05.011 -
Acta Neuropathologica May 2024
From metabolomics to proteomics: understanding the role of dopa decarboxylase in Parkinson's disease. Scientific commentary on: "Comprehensive proteomics of CSF, plasma, and urine identify DDC and other biomarkers of early Parkinson's disease".
Topics: Humans; Parkinson Disease; Proteomics; Biomarkers; Metabolomics; Dopa Decarboxylase
PubMed: 38761253
DOI: 10.1007/s00401-024-02739-5 -
The Lancet. Neurology Jun 2024
Topics: Humans; Parkinson Disease; Deferiprone; Antiparkinson Agents; Pyridones; Iron Chelating Agents; Negative Results; Clinical Trials as Topic
PubMed: 38760092
DOI: 10.1016/S1474-4422(24)00163-7 -
The Lancet. Neurology Jun 2024
Topics: Humans; Parkinson Disease; Deferiprone; Antiparkinson Agents; Iron Chelating Agents; Pyridones; Negative Results; Randomized Controlled Trials as Topic
PubMed: 38760091
DOI: 10.1016/S1474-4422(24)00097-8 -
International Journal of Biological... Jun 2024Ropinirole (ROP) is a dopamine agonist that can cross the blood-brain barrier (BBB), which is crucial for drugs targeting neurological conditions like Alzheimer's...
Ropinirole (ROP) is a dopamine agonist that can cross the blood-brain barrier (BBB), which is crucial for drugs targeting neurological conditions like Alzheimer's disease (AD). The rationale for the current research is to investigate the potential of ROP as an inhibitor of Microtubule affinity regulating kinase 4 (MARK4)-NFκβ in neurodegenerative diseases, specifically AD. The interaction between ROP and MARK4-NFκβ holds significant promise in the realm of drug discovery and therapeutic interventions for diseases like AD. Molecular docking and biophysical characterization demonstrate how ROP effectively hinders MARK4 activity, offering detailed insights into their molecular interactions. The present research also investigates the biological aspect of MARK4 shows promise in treating AD, with neuroinflammation playing a crucial role in the disease's progression. Aβ and ROP were co-administered directly into the cells for the establishment of the AD model. We confirmed that ROP can inhibit the path of MARK4 activity, as evidenced by biophysical characterization, and can enhance the cell viability, lowers the expression of MARK4, decrease the rate of oxidative stress, and attenuate the expression of NFκβ, leading to reduced neuronal apoptosis in an in vitro-induced Aβ model. Overall, this research provides valuable mechanistic insights into the neuroprotective potential of ROP and its ability to target the MARK4-NFκβ pathway.
Topics: Alzheimer Disease; Humans; NF-kappa B; Signal Transduction; Protein Serine-Threonine Kinases; Indoles; Molecular Docking Simulation; Amyloid beta-Peptides; Oxidative Stress; Neuroinflammatory Diseases; Apoptosis; Cell Survival; Down-Regulation; Animals
PubMed: 38759860
DOI: 10.1016/j.ijbiomac.2024.132425 -
Cell Reports. Medicine Jun 2024Levodopa-induced dyskinesia (LID) is an intractable motor complication arising in Parkinson's disease with the progression of disease and chronic treatment of levodopa....
Levodopa-induced dyskinesia (LID) is an intractable motor complication arising in Parkinson's disease with the progression of disease and chronic treatment of levodopa. However, the specific cell assemblies mediating dyskinesia have not been fully elucidated. Here, we utilize the activity-dependent tool to identify three brain regions (globus pallidus external segment [GPe], parafascicular thalamic nucleus, and subthalamic nucleus) that specifically contain dyskinesia-activated ensembles. An intensity-dependent hyperactivity in the dyskinesia-activated subpopulation in GPe (GPe) is observed during dyskinesia. Optogenetic inhibition of GPe significantly ameliorates LID, whereas reactivation of GPe evokes dyskinetic behavior in the levodopa-off state. Simultaneous chemogenetic reactivation of GPe and another previously reported ensemble in striatum fully reproduces the dyskinesia induced by high-dose levodopa. Finally, we characterize GPe as a subset of prototypic neurons in GPe. These findings provide theoretical foundations for precision medication and modulation of LID in the future.
Topics: Levodopa; Globus Pallidus; Dyskinesia, Drug-Induced; Animals; Neurons; Male; Optogenetics; Mice; Parkinson Disease; Humans; Subthalamic Nucleus
PubMed: 38759649
DOI: 10.1016/j.xcrm.2024.101566 -
Medicine May 2024This study aims to investigate the effect of amantadine use on neurological outcomes and mortality in patients with severe traumatic brain injury (TBI) (Glasgow coma... (Observational Study)
Observational Study
This study aims to investigate the effect of amantadine use on neurological outcomes and mortality in patients with severe traumatic brain injury (TBI) (Glasgow coma score [GCS] between 3 and 8) who have been followed up on mechanical ventilators in the intensive care unit (ICU). Data from the hospital's electronic records were retrospectively searched. Patients over 18 years of age, with severe brain trauma (GCS between 3-8), who were treated with endotracheal intubation and invasive mechanical ventilation at admission to the ICU, and who were treated with Amantadine hydrochloride at least once in the first week of follow-up were included in the study. To evaluate the patients' neurological outcomes, the GCS and FOUR scores were used. GCS and FOUR scores were recorded on the 1st, 3rd, and 7th days of the first week. In addition, the score difference between the 1st and 7th day was calculated for both scores. The patients were divided into 2 groups: those receiving amantadine treatment (Group A, n = 44) and the control group (Group C, n = 47). The median age of all patients was 39 (18-81) (P = .425). When Group A and Group C were compared, no statistically significant results were found between the 1st, 3rd, and 7th day GCS values (P = .474, P = .483, and P = 329, respectively). However, the difference in GCS values between day 1 and day 7 (∆ GCS 7-1) was statistically significant (P = .012). Similarly, when Group A and Group C were compared, no statistically significant results were found between the 1st, 3rd, and 7th day FOUR score values (P = .948, P = .471, and P = .057, respectively). However, the FOUR score values between day 1 and day 7 (∆ FOUR score 7-1) were statistically significant (P = .004). There was no statistically significant difference among the groups in terms of ICU length of stay, duration of non-ICU hospital stay, and length of hospital stay (P = .222, P = .175, and P = .067, respectively). Amantadine hydrochloride may help improve neurological outcomes in patients with severe TBI. However, further research is needed to investigate this topic.
Topics: Humans; Amantadine; Respiration, Artificial; Male; Female; Middle Aged; Adult; Retrospective Studies; Intensive Care Units; Aged; Glasgow Coma Scale; Adolescent; Aged, 80 and over; Brain Injuries, Traumatic; Young Adult; Treatment Outcome; Craniocerebral Trauma
PubMed: 38758901
DOI: 10.1097/MD.0000000000038172 -
Journal of Materials Chemistry. B Jun 2024Liposome-based technologies derived from lipids and polymers (, PEGylated liposomes) have been recognized because of their applications in nanomedicine. However, since...
Liposome-based technologies derived from lipids and polymers (, PEGylated liposomes) have been recognized because of their applications in nanomedicine. However, since such systems represent myriad challenges and may promote immune responses, investigation of new biomaterials is mandatory. Here, we report on a biophysical investigation of liposomes decorated with bioconjugated copolymers in the presence (or absence) of amantadine (an antiviral medication). First, copolymers of poly(,-dimethylacrylamide--fluoresceinacrylate--acrylic acid--succinimide ester)--poly(-isopropylacrylamide) (PDMA--PNIPAM) containing a fluorescence label were biofunctionalized with short peptides that resemble the sequence of the loops 220 and 130 of the binding receptor of the hemagglutinin (HA) protein of the influenza A virus. Then, the bioconjugated copolymers were self-assembled along with liposomes composed of 1,2 dimyristoyl--3-phosphocholine, sphingomyelin, and cholesterol (MSC). These biohybrid systems, with and without amantadine, were systematically characterized using differential scanning calorimetry (DSC), dynamic light scattering (DLS), and cryogenic transmission electron microscopy (cryoTEM). Finally, the systems were tested in an study to evaluate cytotoxicity and direct immunofluorescence in Madin Darbin Canine Kidney (MDCK) cells. The biohybrid systems displayed long-term stability, thermo-responsiveness, hydrophilic-hydrophobic features, and fluorescence properties and were presumable endowed with cell targeting properties intrinsically integrated into the amino acid sequences of the utilized peptides, which indeed turn them into promising nanodevices for biomedical applications.
Topics: Liposomes; Amantadine; Polymers; Animals; Antiviral Agents; Madin Darby Canine Kidney Cells; Dogs
PubMed: 38757473
DOI: 10.1039/d4tb00171k -
ACS Sensors May 2024Cu accelerates the viral-like propagation of α-synuclein fibrils and plays a key role in the pathogenesis of Parkinson's disease (PD). Therefore, the accurate detection...
Cu accelerates the viral-like propagation of α-synuclein fibrils and plays a key role in the pathogenesis of Parkinson's disease (PD). Therefore, the accurate detection of Cu is essential for the diagnosis of PD and other neurological diseases. The Cu detection process is impeded by substances that have similar electrochemical properties. In this study, graphdiyne (GDY), a new kind of carbon allotrope with strong electron-donating ability, was utilized for the highly selective detection of Cu by taking advantage of its outstanding adsorption capacity for Cu. Density functional theory (DFT) calculations show that Cu atoms are adsorbed in the cavity of GDY, and the absorption energy between Cu and C atoms is higher than that of graphene (GR), indicating that the cavity of GDY is favorable for the adsorption of Cu atoms and electrochemical sensing. The GDY-based electrochemical sensor can effectively avoid the interference of amino acids, metal ions and neurotransmitters and has a high sensitivity of 9.77 μA·μM·cm, with a minimum detectable concentration of 200 nM. During the investigating pathogenesis and therapeutic process of PD with α-synuclein as the diagnostic standard, the concentration of Cu in cells before and after L-DOPA and GSH treatments were examined, and it was found that Cu exhibits high potential as a biomarker for PD. This study not only harnesses the favorable adsorption of the GDY and Cu to improve the specificity of ion detection but also provide clues for deeper understanding of the role of Cu in neurobiology and neurological diseases.
Topics: Copper; Parkinson Disease; Graphite; Humans; Electrochemical Techniques; alpha-Synuclein; Density Functional Theory; Levodopa; Limit of Detection; Glutathione
PubMed: 38752502
DOI: 10.1021/acssensors.4c00633