scholarly journals Potential Application of Yokukansan as a Remedy for Parkinson’s Disease

2018 ◽  
Vol 2018 ◽  
pp. 1-19
Author(s):  
Jung-Hee Jang ◽  
Kyungsook Jung ◽  
Joong-Sun Kim ◽  
Inchul Jung ◽  
Horyong Yoo ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Clinical Efficacy ◽  
Sleep Disturbances ◽  
Clinical Symptoms ◽  
Neurodegenerative Disorder ◽  
Psychological Symptoms ◽  
Nonmotor Symptoms ◽  
Neuroprotective Effects ◽  
Complementary And Alternative

Parkinson’s disease (PD), the second most common progressive neurodegenerative disorder, is characterized by complex motor and nonmotor symptoms. The clinical diagnosis of PD is defined by bradykinesia and other cardinal motor features, although several nonmotor symptoms are also related to disability, an impaired quality of life, and shortened life expectancy. Levodopa, which is used as a standard pharmacotherapy for PD, has limitations including a short half-life, fluctuations in efficacy, and dyskinesias with long-term use. There have been efforts to develop complementary and alternative therapies for incurable PD. Yokukansan (YKS) is a traditional herbal medicine that is widely used for treating neurosis, insomnia, and night crying in children. The clinical efficacy of YKS for treating behavioral and psychological symptoms, such as delusions, hallucinations, and impaired agitation/aggression subscale and activities of daily living scores, has mainly been investigated in the context of neurological disorders such as PD, Alzheimer’s disease, and other psychiatric disorders. Furthermore, YKS has previously been found to improve clinical symptoms, such as sleep disturbances, neuropsychiatric and cognitive impairments, pain, and tardive dyskinesia. Preclinical studies have reported that the broad efficacy of YKS for various symptoms involves its regulation of neurotransmitters including GABA, serotonin, glutamate, and dopamine, as well as the expression of dynamin and glutamate transporters, and changes in glucocorticoid hormones and enzymes such as choline acetyltransferase and acetylcholinesterase. Moreover, YKS has neuroprotective effects at various cellular levels via diverse mechanisms. In this review, we focus on the clinical efficacy and neuropharmacological effects of YKS. We discuss the possible mechanisms underpinning the effects of YKS on neuropathology and suggest that the multiple actions of YKS may be beneficial as a treatment for PD. We highlight the potential that YKS may serve as a complementary and alternative strategy for the treatment of PD.

Changes in Nonmotor Symptoms Following an 8-Week Yoga Intervention for People with Parkinson's Disease

2019 ◽  
Vol 29 (1) ◽  
pp. 91-99 ◽  
Author(s):  
Alysha A. Walter ◽  
Em V. Adams ◽  
Marieke Van Puymbroeck ◽  
Brandi M. Crowe ◽  
Enrique Urrea-Mendoza ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Sleep Disturbances ◽  
Neurodegenerative Disorder ◽  
Nonmotor Symptoms ◽  
Yoga Intervention ◽  
Balance Confidence ◽  
Related Quality

Abstract Parkinson's disease (PD) is a neurodegenerative disorder marked by progressive degenerative motor symptoms (e.g., tremors, impaired balance and gait) and nonmotor symptoms (e.g., fatigue, sleep disturbances, pain) that can negatively influence health-related quality of life (HRQoL). Previous studies have shown that yoga for individuals with PD improves balance, strength, and mobility. However, little research has been conducted to determine the effect of yoga on nonmotor symptoms of PD. The purpose of this study was to examine changes in nonmotor symptoms among individuals with PD following an 8-week yoga intervention. Data used for analyses were part of a larger study that researched improvements in motor function for individuals with PD. Participants (N = 27) were randomly assigned to experimental (n = 15) and control (n = 12) groups and completed pre- and postintervention quantitative measures. Within-group improvements were statistically significant for fatigue measured by the Parkinson's Fatigue Scale, balance confidence measured by the Activities Balance Confidence Scale, the belief in one's ability to manage falls measured by the Falls Management Scale, activity constraints measured by the Activities Constraint Questionnaire, and PD-specific quality of life measured by the Parkinson's Disease Questionnaire-8. Across-group changes were statistically significant for activity constraints. Findings indicate yoga may be an efficacious intervention for improving nonmotor symptoms as well as HRQoL for individuals with PD.

Neuroprotective Effects of a GLP-2 Analogue in the MPTP Parkinson’s Disease Mouse Model

2021 ◽  
pp. 1-15
Author(s):  
Zijuan Zhang ◽  
Li Hao ◽  
Ming Shi ◽  
Ziyang Yu ◽  
Simai Shao ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Substantia Nigra ◽  
Mouse Model ◽  
Neurodegenerative Disorder ◽  
Enzyme Linked Immunosorbent Assay ◽  
Protective Effects ◽  
Neuroprotective Effects ◽  
Expression Levels ◽  
Dual Agonist

Background: Glucagon-like peptide 2 (GLP-2) is a peptide hormone derived from the proglucagon gene expressed in the intestines, pancreas and brain. Some previous studies showed that GLP-2 improved aging and Alzheimer’s disease related memory impairments. Parkinson’s disease (PD) is a progressive neurodegenerative disorder, and to date, there is no particular medicine reversed PD symptoms effectively. Objective: The aim of this study was to evaluate neuroprotective effects of a GLP-2 analogue in the 1-Methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) PD mouse model. Methods: In the present study, the protease resistant Gly(2)-GLP-2 (50 nmol/kg ip.) analogue has been tested for 14 days by behavioral assessment, transmission electron microscope, immunofluorescence histochemistry, enzyme-linked immunosorbent assay and western blot in an acute PD mouse model induced by MPTP. For comparison, the incretin receptor dual agonist DA5-CH was tested in a separate group. Results: The GLP-2 analogue treatment improved the locomotor and exploratory activity of mice, and improved bradykinesia and movement imbalance of mice. Gly(2)-GLP-2 treatment also protected dopaminergic neurons and restored tyrosine hydroxylase expression levels in the substantia nigra. Gly(2)-GLP-2 furthermore reduced the inflammation response as seen in lower microglia activation, and decreased NLRP3 and interleukin-1β pro-inflammatory cytokine expression levels. In addition, the GLP-2 analogue improved MPTP-induced mitochondrial dysfunction in the substantia nigra. The protective effects were comparable to those of the dual agonist DA5-CH. Conclusion: The present results demonstrate that Gly(2)-GLP-2 can attenuate NLRP3 inflammasome-mediated inflammation and mitochondrial damage in the substantia nigra induced by MPTP, and Gly(2)-GLP-2 shows neuroprotective effects in this PD animal model.

scholarly journals Peptide TFP5/TP5 derived from Cdk5 activator P35 provides neuroprotection in the MPTP model of Parkinson’s disease

2015 ◽  
Vol 26 (24) ◽  
pp. 4478-4491 ◽  
Author(s):  
BK. Binukumar ◽  
Varsha Shukla ◽  
Niranjana D. Amin ◽  
Philip Grant ◽  
M. Bhaskar ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neurodegenerative Disorder ◽  
Neuroprotective Effect ◽  
Selective Inhibition ◽  
Motor Dysfunction ◽  
Dopamine Neurons ◽  
Dopamine Depletion ◽  
Neuroprotective Effects

Parkinson’s disease (PD) is a chronic neurodegenerative disorder characterized by the loss of dopamine neurons in the substantia nigra, decreased striatal dopamine levels, and consequent extrapyramidal motor dysfunction. Recent evidence indicates that cyclin-dependent kinase 5 (Cdk5) is inappropriately activated in several neurodegenerative conditions, including PD. To date, strategies to specifically inhibit Cdk5 hyperactivity have not been successful without affecting normal Cdk5 activity. Previously we reported that TFP5 peptide has neuroprotective effects in animal models of Alzheimer’s disease. Here we show that TFP5/TP5 selective inhibition of Cdk5/p25 hyperactivation in vivo and in vitro rescues nigrostriatal dopaminergic neurodegeneration induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP/MPP+) in a mouse model of PD. TP5 peptide treatment also blocked dopamine depletion in the striatum and improved gait dysfunction after MPTP administration. The neuroprotective effect of TFP5/TP5 peptide is also associated with marked reduction in neuroinflammation and apoptosis. Here we show selective inhibition of Cdk5/p25 ­hyperactivation by TFP5/TP5 peptide, which identifies the kinase as a potential therapeutic target to reduce neurodegeneration in Parkinson’s disease.

scholarly journals Amelioration of Mitochondrial Quality Control and Proteostasis by Natural Compounds in Parkinson’s Disease Models

2019 ◽  
Vol 20 (20) ◽  
pp. 5208 ◽  
Author(s):  
Bongki Cho ◽  
Taeyun Kim ◽  
Yu-Jin Huh ◽  
Jaemin Lee ◽  
Yun-Il Lee
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mitochondrial Dysfunction ◽  
Neurodegenerative Disorder ◽  
Ubiquitin Proteasome System ◽  
Natural Compounds ◽  
Cellular Damage ◽  
Pathophysiological Mechanism ◽  
Neuroprotective Effects ◽  
Age Related

Parkinson’s disease (PD) is a well-known age-related neurodegenerative disorder associated with longer lifespans and rapidly aging populations. The pathophysiological mechanism is a complex progress involving cellular damage such as mitochondrial dysfunction and protein homeostasis. Age-mediated degenerative neurological disorders can reduce the quality of life and also impose economic burdens. Currently, the common treatment is replacement with levodopa to address low dopamine levels; however, this does not halt the progression of PD and is associated with adverse effects, including dyskinesis. In addition, elderly patients can react negatively to treatment with synthetic neuroprotection agents. Recently, natural compounds such as phytochemicals with fewer side effects have been reported as candidate treatments of age-related neurodegenerative diseases. This review focuses on mitochondrial dysfunction, oxidative stress, hormesis, proteostasis, the ubiquitin‒proteasome system, and autophagy (mitophagy) to explain the neuroprotective effects of using natural products as a therapeutic strategy. We also summarize the efforts to use natural extracts to develop novel pharmacological candidates for treatment of age-related PD.

scholarly journals Parkinson's Disease and Sleep/Wake Disturbances

2012 ◽  
Vol 2012 ◽  
pp. 1-14 ◽  
Author(s):  
Todd J. Swick
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Sleep Disorders ◽  
Sleep Disturbances ◽  
Treatment Options ◽  
Rem Sleep Behavior Disorder ◽  
Behavior Disorder ◽  
Clinical Aspects ◽  
Nonmotor Symptoms ◽  
Sleep Behavior

Parkinson's disease (PD) has traditionally been characterized by its cardinal motor symptoms of bradykinesia, rigidity, resting tremor, and postural instability. However, PD is increasingly being recognized as a multidimensional disease associated with myriad nonmotor symptoms including autonomic dysfunction, mood disorders, cognitive impairment, pain, gastrointestinal disturbance, impaired olfaction, psychosis, and sleep disorders. Sleep disturbances, which include sleep fragmentation, daytime somnolence, sleep-disordered breathing, restless legs syndrome (RLS), nightmares, and rapid eye movement (REM) sleep behavior disorder (RBD), are estimated to occur in 60% to 98% of patients with PD. For years nonmotor symptoms received little attention from clinicians and researchers, but now these symptoms are known to be significant predictors of morbidity in determining quality of life, costs of disease, and rates of institutionalization. A discussion of the clinical aspects, pathophysiology, evaluation techniques, and treatment options for the sleep disorders that are encountered with PD is presented.

scholarly journals Neuroprotective Effect of Curcumin on the Nigrostriatal Pathway in a 6-Hydroxydopmine-Induced Rat Model of Parkinson’s Disease is Mediated by α7-Nicotinic Receptors

2020 ◽  
Vol 21 (19) ◽  
pp. 7329
Author(s):  
Eslam El Nebrisi ◽  
Hayate Javed ◽  
Shreesh K Ojha ◽  
Murat Oz ◽  
Safa Shehab
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Rat Model ◽  
Dopaminergic Neurons ◽  
Motor Behavior ◽  
Neurodegenerative Disorder ◽  
Neuroprotective Effect ◽  
Intraperitoneal Administration ◽  
Neuroprotective Effects ◽  
Α7 Nachr

Parkinson’s disease (PD) is a common neurodegenerative disorder, characterized by selective degeneration of dopaminergic nigrostriatal neurons. Most of the existing pharmacological approaches in PD consider replenishing striatal dopamine. It has been reported that activation of the cholinergic system has neuroprotective effects on dopaminergic neurons, and human α7-nicotinic acetylcholine receptor (α7-nAChR) stimulation may offer a potential therapeutic approach in PD. Our recent in-vitro studies demonstrated that curcumin causes significant potentiation of the function of α7-nAChRs expressed in Xenopus oocytes. In this study, we conducted in vivo experiments to assess the role of the α7-nAChR on the protective effects of curcumin in an animal model of PD. Intra-striatal injection of 6-hydroxydopmine (6-OHDA) was used to induce Parkinsonism in rats. Our results demonstrated that intragastric curcumin treatment (200 mg/kg) significantly improved the abnormal motor behavior and offered neuroprotection against the reduction of dopaminergic neurons, as determined by tyrosine hydroxylase (TH) immunoreactivity in the substantia nigra and caudoputamen. The intraperitoneal administration of the α7-nAChR-selective antagonist methyllycaconitine (1 µg/kg) reversed the neuroprotective effects of curcumin in terms of both animal behavior and TH immunoreactivity. In conclusion, this study demonstrates that curcumin has a neuroprotective effect in a 6-hydroxydopmine (6-OHDA) rat model of PD via an α7-nAChR-mediated mechanism.

scholarly journals Nonmotor Symptoms Groups in Parkinson's Disease Patients: Results of a Pilot, Exploratory Study

2011 ◽  
Vol 2011 ◽  
pp. 1-5 ◽  
Author(s):  
Santiago Perez Lloret ◽  
Malco Rossi ◽  
Marcelo Merello ◽  
Olivier Rascol ◽  
Daniel P. Cardinali
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Sleep Disturbances ◽  
Tricyclic Antidepressants ◽  
Rating Scale ◽  
Neuropsychiatric Symptoms ◽  
Depression Scale ◽  
Nonmotor Symptoms ◽  
Wearing Off ◽  
Urogenital Symptoms

Nonmotor symptoms (NMS) like neuropsychiatric symptoms, sleep disturbances or autonomic symptoms are a common feature of Parkinson's disease (PD). To explore the existence of groups of NMS and to relate them to PD characteristics, 71 idiopathic non-demented PD out-patients were recruited. Sleep was evaluated by the PD Sleep Scale (PDSS). Several neuropsychiatric, gastrointestinal and urogenital symptoms were obtained from the NMSQuest. Sialorrhea or dysphagia severity was obtained from the Unified PD Rating Scale activities of daily living section. MADRS depression scale was also administered. Exploratory factor analysis revealed the presence of 5 factors, explaining 70% of variance. The first factor included PDSS measurement of sleep quality, nocturnal restlessness, off-related problems and daytime somnolence; the second factor included nocturia (PDSS) and nocturnal activity; the third one included gastrointestinal and genitourinary symptoms; the forth one included nocturnal psychosis (PDSS), sialorrhea and dysphagia (UPDRS); and the last one included the MADRS score as well as neuropsychiatric symptoms. Sleep disorders correlated with presence of wearing-off, nocturia with age >69 years, and nocturnal psychosis with levodopa equivalent dose or UPDRS II score. Neuropsychiatric symptoms correlated with UPDRS II+III score and non-tricyclic antidepressants. These results support the occurrence of significant NMS grouping in PD patients.

scholarly journals Tetramethylpyrazine Analogue T-006 Exerts Neuroprotective Effects against 6-Hydroxydopamine-Induced Parkinson’s Disease In Vitro and In Vivo

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Hefeng Zhou ◽  
Min Shao ◽  
Xuanjun Yang ◽  
Chuwen Li ◽  
Guozhen Cui ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Motor Coordination ◽  
Neurodegenerative Disorder ◽  
Nerve Fibers ◽  
Substantia Nigra Pars Compacta ◽  
Neuroprotective Effects ◽  
6 Hydroxydopamine

Parkinson’s disease (PD) is a neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc), and there is no cure for it at present. We have previously reported that the tetramethylpyrazine (TMP) derivative T-006 exhibited beneficial effects in Alzheimer’s disease (AD) models. However, its effect on PD remains unclear. In the present study, we investigated the neuroprotective effects and underlying mechanisms of T-006 against 6-hydroxydopamine- (6-OHDA-) induced lesions in in vivo and in vitro PD models. Our results demonstrated that T-006 alleviated mitochondrial membrane potential loss and restored the energy metabolism and mitochondrial biogenesis that were induced by 6-OHDA in PC12 cells. In addition, animal experiments showed that administration of T-006 significantly attenuated the 6-OHDA-induced loss of tyrosine hydroxylase- (TH-) positive neurons in the SNpc, as well as dopaminergic nerve fibers in the striatum, and also increased the concentration of dopamine and its metabolites (DOPAC, HVA) in the striatum. Functional deficits were restored following T-006 treatment in 6-OHDA-lesioned mice, as demonstrated by improved motor coordination and rotational behavior. In addition, we found that the neuroprotective effects of T-006 were mediated, at least in part, by the activation of both the PKA/Akt/GSK-3β and CREB/PGC-1α/NRF-1/TFAM pathways. In summary, our findings demonstrate that T-006 could be developed as a novel neuroprotective agent for PD, and the two pathways might be promising therapeutic targets for PD.

scholarly journals Clinical Features of Parkinson’s Disease: The Evolution of Critical Symptoms

Biology ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 103 ◽  
Author(s):  
Csaba Váradi
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neurodegenerative Disorder ◽  
Successful Implementation ◽  
Current Clinical Practice ◽  
Clinical Markers ◽  
Nonmotor Symptoms ◽  
Potential Patient ◽  
Targeted Detection ◽  
Neuroprotective Therapies

Parkinson’s disease (PD) is a multi-attribute neurodegenerative disorder combining motor and nonmotor symptoms without well-defined diagnostic clinical markers. The presence of primary motor features (bradykinesia, rest tremor, rigidity and loss of postural reflexes) are the most characteristic signs of PD that are also utilized to identify patients in current clinical practice. The successful implementation of levodopa treatment revealed that nonmotor features are the main contributors of patient disability in PD, and their occurrence might be earlier than motor symptoms during disease progression. Targeted detection of prodromal PD symptoms can open up new possibilities in the identification of PD patients and provide potential patient populations for developing novel neuroprotective therapies. In this review, the evolution of critical features in PD diagnosis is described with special attention to nonmotor symptoms and their possible detection.

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