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1.
J Photochem Photobiol B ; 200: 111635, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31671372

RESUMO

Parkinson disease is one of the most common neurological movement disorders affecting geriatric population. Biosynthesized gold nanoparticles are the ideal alternatives spotlighted by many researchers to treat various diseases. In the present study we synthesized gold nanoparticles using the root extract of Paeonia mountan, woody trees which are used in traditional Chinese medicine to be prescribed for diverse diseases. The synthesis of gold nanoparticles was confirmed with UV-Vis spectroscopic analysis and characterized using FTIR, HR-TEM, EDAX and XRD analysis. The cytotoxicity property of synthesized gold nanoparticles was assessed using MTT assay in the murine microglial BV2 cells. The neuroprotective effect of synthesized gold nanoparticles in inflammatory agent lipopolysaccharides triggered murine microglial BV2 cells was evaluated using nitric oxide, prostaglandin E2 and inflammatory cytokines assays such as IL-6&IL-1ß. Further to confirm in vivo effect of synthesized nanoparticles, the nanoparticles were treated to Parkinson induced C57BL/6 mice. Behavioral, biochemical and molecular analysis were performed to estimate the potency of synthesized gold nanoparticles against the Parkinson induction in mice model. Our characterization results prove the gold nanoparticles synthesized using Paeonia mountan fulfills the requirement of ideal nanodrug and it potentially inhibited the inflammation in in vitro murine microglial BV2. The results of in vivo experiments authentically confirm gold nanoparticles synthesized using Paeonia mountan alleviates the neuroinflammation and improves the motor coordination in Parkinson induced mice.


Assuntos
Ouro/química , Nanopartículas Metálicas/química , Fármacos Neuroprotetores/química , Paeonia/química , Extratos Vegetais/química , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Antioxidantes/química , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Citocinas/metabolismo , Química Verde , Lipopolissacarídeos/farmacologia , Masculino , Nanopartículas Metálicas/uso terapêutico , Nanopartículas Metálicas/toxicidade , Camundongos , Camundongos Endogâmicos C57BL , Microglia/citologia , Microglia/efeitos dos fármacos , Microglia/metabolismo , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Óxido Nítrico/metabolismo , Paeonia/metabolismo , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/patologia , Doença de Parkinson/veterinária , Raízes de Plantas/química , Raízes de Plantas/metabolismo
2.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 35(9): 794-799, 2019 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-31750820

RESUMO

Objective To explore the inhibitory effects of polyphenols from Toona sinensis seeds (PTSS) on neuroinflammation and the underlying mechanism in rats with Parkinson's disease (PD). Methods PD rat models were prepared by stereotaxic injection of 6-hydroxydopamine (6-OHDA) into one side of striatum of Sprague-Dawley male rats. Model rats were randomly divided into model group and PTSS group (n=10), and a normal control group was set as well (n=10). The rotational behavior of rats was induced by intraperitoneal injection of apomorphine (APO) after 30 days, and the behavioral changes of rats from each group were investigated. The morphological and quantity changes of DA neurons (tyrosine hydroxylase positive, TH-positive), microglia cells (ionized calcium binding adaptor molecule-1, Iba1-positive) and astrocytes (glial fibrillary acidic protein, GFAP-positive) in substantia nigra (SN) of rats from each group were examined by immunohistochemistry. Inducible nitric oxide synthase (iNOS), nuclear factor-κB p65 (NF-κBp65), p38 mitogen-activated protein kinase (p38MAPK) and phosphor-p38 mitogen-activated protein kinase (p-p38MAPK) levels were evaluated through immunohistochemical staining. The protein levels of TH, GFAP, p38MAPK and p-p38MAPK in SN were examined by Western blot analysis. Results The number of rotations in the rats of the PTSS group was significantly reduced compared with that in the model group. The number of TH-positive cells in the model group was much less than that in the control group. The number and protein levels of TH-positive cells were enhanced significantly by PTSS intervention. Compared with the control group, the protein levels of Iba1, GFAP, iNOS, NF-κB, p38MAPK and p-p38MAPK in the injured side of the model group significantly increased, which could be suppressed significantly by PTSS intervention. Conclusion PTSS demonstrates protective effects on DA neurons by inhibiting p38MAPK signaling pathway and reducing the expression of inflammatory factors in PD rats.


Assuntos
Neurônios Dopaminérgicos/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases , Meliaceae/química , Doença de Parkinson/tratamento farmacológico , Polifenóis/farmacologia , Sementes/química , Animais , Masculino , Oxidopamina , Compostos Fitoquímicos/farmacologia , Ratos , Ratos Sprague-Dawley , Substância Negra
3.
Brain Nerve ; 71(9): 953-959, 2019 Sep.
Artigo em Japonês | MEDLINE | ID: mdl-31506397

RESUMO

Among the therapeutic agents for Parkinson's disease (PD), there are important drugs that precede drug repositioning. Amantadine, developed as a treatment for influenza A, has been long used as a treatment for PD. Zonisamide is an antiepileptic drug developed in Japan, where its therapeutic effects on PD were also discovered and developed. In recent years, dabrafenib, a therapeutic agent for malignant melanoma, has bean identified as a potential therapeutic agent for PD. Amantadine and zonisamide are drugs that have been serendipitously developed in clinical settings for patients with PD. Meanwhile, the potential for repurposing dabrafenib was discovered by utilizing the results of genome-wide association studies, drug databases, and protein-protein interaction databases.


Assuntos
Amantadina/uso terapêutico , Antiparkinsonianos/uso terapêutico , Imidazóis/uso terapêutico , Oximas/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Zonisamida/uso terapêutico , Reposicionamento de Medicamentos , Estudo de Associação Genômica Ampla , Humanos
5.
Neurol Neurochir Pol ; 53(4): 291-295, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31441493

RESUMO

AIM OF THE STUDY: Postural deformities are common in Parkinson's disease (PD) patients. Several treatment options have been reported, but responses to these treatments appear unpredictable. Istradefylline is a novel drug for PD. Cases of PD patients whose postural deformities were improved after withdrawal of dopamine agonists and initiation of istradefylline are presented. MATERIALS AND METHODS: Four consecutive patients with postural deformities including antecollis, Pisa syndrome, and camptocormia were recruited and treated with istradefylline in combination with withdrawal of dopamine agonists, which are possible causes of postural deformities. RESULTS: The dopamine agonists were discontinued an average of 26 months after the development of the postural deformities, and istradefylline was initiated an average of 1.3 months after dopamine agonist withdrawal. Three patients with preserved paraspinal muscle volume showed good responses to the treatment regimen at least two months after dopamine agonist withdrawal. CONCLUSIONS AND CLINICAL IMPLICATIONS: Postural deformities caused by dopamine agonists generally improve less than two weeks after dopamine agonist withdrawal. Given the response time in the present study, the response was unlikely to be caused solely by dopamine agonist withdrawal. Istradefylline can be a potential therapeutic option; however, appropriate selection of patients for treatment with istradefylline is warranted.


Assuntos
Atrofia Muscular Espinal , Doença de Parkinson , Purinas/uso terapêutico , Curvaturas da Coluna Vertebral , Humanos , Doença de Parkinson/tratamento farmacológico
6.
Neurol Neurochir Pol ; 53(4): 239-241, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31469906

RESUMO

INTRODUCTION: In the current edition, Fujioka and colleagues report on four Japanese patients with Parkinson disease (PD) and severe postural abnormalities treated with istradefylline (adenosine A2A receptor antagonist); further, dopamine agonists were with- drawn. Three patients experienced significant improvements of postural abnormalities. CLINICAL REFLECTIONS: Postural abnormalities in PD include camptocormia, antecollis, lateral trunk flexion, and scoliosis. They may be very pronounced and significantly reduce quality of life. The therapy of postural deformities in PD is currently disappointing. CLINICAL IMPLICATIONS: Effective therapeutic strategies for postural deformities in PD are an unmet need. Larger clinical trials investigating novel approaches including istradefylline are warranted.


Assuntos
Doença de Parkinson , Purinas/uso terapêutico , Antagonistas do Receptor A2 de Adenosina , Humanos , Doença de Parkinson/tratamento farmacológico , Qualidade de Vida
7.
Nature ; 571(7766): 565-569, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31316206

RESUMO

Parkinson's disease is a neurodegenerative disorder with motor symptoms linked to the loss of dopaminergic neurons in the substantia nigra compacta. Although the mechanisms that trigger the loss of dopaminergic neurons are unclear, mitochondrial dysfunction and inflammation are thought to have key roles1,2. An early-onset form of Parkinson's disease is associated with mutations in the PINK1 kinase and PRKN ubiquitin ligase genes3. PINK1 and Parkin (encoded by PRKN) are involved in the clearance of damaged mitochondria in cultured cells4, but recent evidence obtained using knockout and knockin mouse models have led to contradictory results regarding the contributions of PINK1 and Parkin to mitophagy in vivo5-8. It has previously been shown that PINK1 and Parkin have a key role in adaptive immunity by repressing presentation of mitochondrial antigens9, which suggests that autoimmune mechanisms participate in the aetiology of Parkinson's disease. Here we show that intestinal infection with Gram-negative bacteria in Pink1-/- mice engages mitochondrial antigen presentation and autoimmune mechanisms that elicit the establishment of cytotoxic mitochondria-specific CD8+ T cells in the periphery and in the brain. Notably, these mice show a sharp decrease in the density of dopaminergic axonal varicosities in the striatum and are affected by motor impairment that is reversed after treatment with L-DOPA. These data support the idea that PINK1 is a repressor of the immune system, and provide a pathophysiological model in which intestinal infection acts as a triggering event in Parkinson's disease, which highlights the relevance of the gut-brain axis in the disease10.


Assuntos
Infecções por Enterobacteriaceae/microbiologia , Infecções por Enterobacteriaceae/fisiopatologia , Intestinos/microbiologia , Doença de Parkinson/genética , Doença de Parkinson/microbiologia , Proteínas Quinases/deficiência , Proteínas Quinases/genética , Animais , Apresentação do Antígeno/imunologia , Autoantígenos/imunologia , Axônios/patologia , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/patologia , Citrobacter rodentium/imunologia , Citrobacter rodentium/patogenicidade , Modelos Animais de Doenças , Neurônios Dopaminérgicos/imunologia , Neurônios Dopaminérgicos/patologia , Infecções por Enterobacteriaceae/imunologia , Infecções por Enterobacteriaceae/patologia , Feminino , Intestinos/imunologia , Intestinos/patologia , Levodopa/uso terapêutico , Masculino , Camundongos , Mitocôndrias/imunologia , Mitocôndrias/patologia , Neostriado/imunologia , Neostriado/microbiologia , Neostriado/patologia , Neostriado/fisiopatologia , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/fisiopatologia , Proteínas Quinases/imunologia , Ubiquitina-Proteína Ligases/deficiência , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/imunologia
8.
Brain Nerve ; 71(8): 857-867, 2019 Aug.
Artigo em Japonês | MEDLINE | ID: mdl-31346142

RESUMO

Over the last few decades, several delayed-start trials have suggested that early introduction of dopamine replacement therapy can improve the prognosis of Parkinson's disease (PD). Moreover, several observations support that L-dopa is non toxic to normal and diseased substantia nigra in humans. Thus, the clinical practice guideline 2018 for PD recommends L-dopa as an initial treatment for PD, in principle. More recently, several potential disease-modifying therapies have been reported to be effective. Furthermore, several recent studies suggest that exercise can be beneficial in delaying disease progression.


Assuntos
Levodopa/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Guias de Prática Clínica como Assunto , Progressão da Doença , Dopamina/uso terapêutico , Exercício , Humanos , Doença de Parkinson/terapia , Substância Negra/fisiopatologia
9.
Expert Opin Pharmacother ; 20(15): 1847-1854, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31290336

RESUMO

Introduction: Pain is a common symptom in Parkinson's disease (PD), impairing quality of life. The clinical appearance and the underlying etiologies are diverse. Different subtypes of pain may occur, with musculoskeletal pain considered to be the most frequent. Often there is also a combination of different causes of pain. There is a lack of controlled studies addressing pain therapy in PD. Areas covered: In this review the authors analyzed the currently available data, taking into account the available publications in the databases, especially PubMed. The authors further provided their expert perspectives on the challenges of treating pain in PD patients. Expert opinion: There is both nociceptive and neuropathic pain and in patients with PD, some PD-related pain and some unrelated. Diagnosis requires a thorough and differentiated history and examination, and targeted diagnostics. Therapeutically, many drugs are used, but the data is unfortunately limited and not specific. Medications used include Parkinson-related, mainly dopaminergic drugs, as well as opioids and non-opioid analgetics, anticonvulsives, antidepressants, and more recently cannabinoids. Currently, therapy is performed nonspecifically, without taking into account the special requirements of PD. Unfortunately, in many cases, pain is resistant to these therapies. In the future, both diagnostic and therapeutic efforts should be made to address this issue.


Assuntos
Analgésicos Opioides/uso terapêutico , Neuralgia/tratamento farmacológico , Manejo da Dor/métodos , Doença de Parkinson/complicações , Doença de Parkinson/tratamento farmacológico , Qualidade de Vida/psicologia , Analgésicos Opioides/farmacologia , Humanos , Doença de Parkinson/patologia
10.
Phytother Res ; 33(9): 2288-2297, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31359520

RESUMO

Parkinson's disease (PD) is a neurodegenerative disease, and the role of neuroinflammation in the pathogenesis and progression of PD has been confirmed. The polysaccharides and triterpenoids of antrodia camphorata (a polyporous fungus) harbor diverse and powerful pharmacological effects. In this study, 6-hydroxydopamine was used to construct a PD mouse model. After antrodia camphorata polysaccharide (ACP) intervention, neurobehavioral changes were detected, neurotransmitter changes in striatum were determined by high-performance liquid chromatography, the alterations of striatal NOD-like receptor pyrin domain containing three (NLRP3) were examined by immunohistochemistry, and the expression of NLRP3, IL-1ß, Caspase-1, and proCaspase-1 were detected by western blot. To be specific, the items of neurobehavioral test included open field activity, rotary test, pole test, gait analysis, and swimming test. As a result, 6-hydroxydopamine could lead to PD-like lesions, including tremor, stiffness, attenuated spontaneous activity, and bradykinesia in mice, and the expression of tyrosine hydroxylase in the striatum was decreased. After ACP intervention, the neuroethology of mice was significantly improved, as demonstrated by the elevated levels of dopamine in the striatum and the decreased expression of dopamine in the striatum in NLRP3 inflammasome. NLRP3 inflammasome played an important role in neuroinflammation in PD mice. ACP could reduce the activation of NLRP3 and expression of related inflammatory factors.


Assuntos
Antrodia/metabolismo , Inflamassomos/metabolismo , Doenças Neurodegenerativas/tratamento farmacológico , Doença de Parkinson/tratamento farmacológico , Animais , Modelos Animais de Doenças , Camundongos , Camundongos Endogâmicos NOD , Doenças Neurodegenerativas/patologia , Doença de Parkinson/patologia , Polissacarídeos
11.
Chem Biol Interact ; 310: 108757, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31323226

RESUMO

Fucoxanthin and fucosterol are archetypal lipid components of edible brown algae that provide several health benefits. Lately, their protective role in Aß1-42-induced cognitive dysfunction in animal models has been reported (Alghazwi et al., 2019; Oh et al., 2018). However, their role in the aminergic system and as a prime treatment approach for multifactorial neurodegenerative diseases still requires exploration. The main aims of the present study are to characterize the role of fucoxanthin and fucosterol in the aminergic pathway via in vitro human monoamine oxidase (hMAO) inhibition and cell-based functional G-protein coupled receptor (GPCR) assays and to underline their possible mechanisms of action via in silico molecular docking studies. Fucoxanthin displayed weak inhibition with IC50 values of 197.41 ±â€¯2.20 and 211.12 ±â€¯1.17 µM over two isoenzymes hMAO-A and hMAO-B, respectively. Fucosterol remained inactive up to 500 µM. In functional assay results, fucoxanthin showed a concentration-dependent agonist effect on dopamine D3 and D4 receptors. The half maximal effective concentration (EC50) of fucoxanthin for dopamine D3 and D4 receptors was 16.87 ±â€¯3.41 and 81.87 ±â€¯6.11 µM, respectively. For dopamine as a reference agonist, the EC50 values for these two receptors were 3.7 and 24 nM, respectively. Fucosterol showed no agonist activity on any of the tested receptors. Similarly, fucoxanthin showed a mild antagonist effect on dopamine D1 and tachykinin (NK1) receptor with inhibition of control agonist response by approximately 40% at 100 µM. Fucosterol displayed mild antagonist effects only on dopamine D1 and D4 receptors. In silico studies revealed potential mechanisms by which fucoxanthin binds to dopamine receptors to exert its agonist effects, including low binding energy and H-bond interactions with Ser196 and Thr115 at the D3 receptor and with Ser196 and Asp115 at the D4 receptor. Our results collectively suggest that fucoxanthin is a potential D3/D4 agonist for the management of neurodegenerative diseases, such as Parkinson's disease.


Assuntos
Doença de Parkinson/tratamento farmacológico , Receptores de Dopamina D3/agonistas , Receptores de Dopamina D4/agonistas , Xantofilas/farmacologia , Sítios de Ligação , Aminas Biogênicas , Humanos , Simulação de Acoplamento Molecular , Doenças Neurodegenerativas/tratamento farmacológico , Neurotransmissores , Feófitas/química , Ligação Proteica , Xantofilas/uso terapêutico
12.
Expert Rev Clin Pharmacol ; 12(7): 681-691, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31159608

RESUMO

Introduction: Parkinson's disease psychosis (PDP) may affect up to 60% of patients with Parkinson's disease over the course of their disease, and is associated with poor prognosis, including increased risks of mortality and nursing home placement. PDP treatments have been limited to off-label use of atypical antipsychotics, most of which pose risks of worsened motor symptoms and other potential adverse events (AEs) due to their dopamine receptor blockade and additional off-target receptor affinities. Pimavanserin is a highly selective 5-HT2A inverse agonist and poses no known risks for worsening of parkinsonism or other off-target receptor AEs. Pimavanserin is the first and only medication approved for PDP treatment. Areas covered: This review covers estimated prevalence, clinical characteristics, diagnostic criteria, and risk factors for PDP; the hypothetical progression of PDP; management of PDP including use of antipsychotics; pharmacology and clinical trial data on pimavanserin; and expert opinion on PDP treatment. The NLM/PubMed database was searched for papers using the search terms of "PDP" AND "treatment" AND "pimavanserin" for the last 10 years. Expert opinion: The recent insights into PDP pathophysiology and approval of the only medication specifically to treat PDP are key advances that should improve the recognition, diagnosis, and management of PDP.


Assuntos
Doença de Parkinson/tratamento farmacológico , Piperidinas/uso terapêutico , Transtornos Psicóticos/tratamento farmacológico , Ureia/análogos & derivados , Antiparkinsonianos/farmacologia , Antiparkinsonianos/uso terapêutico , Antipsicóticos/farmacologia , Antipsicóticos/uso terapêutico , Progressão da Doença , Humanos , Doença de Parkinson/fisiopatologia , Doença de Parkinson/psicologia , Piperidinas/farmacologia , Transtornos Psicóticos/etiologia , Transtornos Psicóticos/fisiopatologia , Fatores de Risco , Agonistas do Receptor 5-HT2 de Serotonina/farmacologia , Agonistas do Receptor 5-HT2 de Serotonina/uso terapêutico , Ureia/farmacologia , Ureia/uso terapêutico
13.
Ideggyogy Sz ; 72(5-6): 187-193, 2019 May 30.
Artigo em Húngaro | MEDLINE | ID: mdl-31241263

RESUMO

Background and purpose: There is relatively few data regarding the usage of dopaminagonists for the treatment of Parkinson's disease; furthermore, there are no publications regarding Central- and Eastern-European countries. The aim of the study was to evaluate the use of dopamine agonists as a therapeutic option amongst Parkinson's disease patients admitted to the Neurological Clinics of Tîrgu Mures during the last 15 years. Methods: In our study we investigated the data of all Parkinson's patients treated at our clinics between the 1st of January 2003 and the 31st of December 2017. We analyzed the particularities of dopamine agonists' usage based on the therapeutic recommendations from the final report of these patients. Regarding time since the diagnosis, we divided the patients in two groups: less than or equal to 5 years and more than 5 years. Results: During the studied period a total of 2379 patients with Parkinson's disease were treated at the Clinics. From the 1237 patients with disease duration under 5 years 665 received dopamine agonists: 120 as monotherapy, 83 together with monoamine oxidase inhibitors and in 234 cases associated with levodopa. The remaining 228 patients were treated with a triple combination of levodopa, dopamine agonists and monoamine oxidase inhibitors. In patients suffering from Parkinson's disease for more than 5 years, in 364 cases out of 653 a dopamine agonist was part of the therapy. Conclusion: The usage of dopamine agonists was similar to the data presented in other studies. We consider that clinicians treating the disease should, with the necessary prudence, use the available and recommended dopamine agonist with the utmost courage to their maximum therapeutic potential.


Assuntos
Antiparkinsonianos/uso terapêutico , Agonistas de Dopamina/uso terapêutico , Levodopa/uso terapêutico , Inibidores da Monoaminoxidase/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Estudos Transversais , Humanos , Resultado do Tratamento
14.
Nurs Educ Perspect ; 40(6): E22-E24, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31232876

RESUMO

The purpose of this study was to increase awareness and educate undergraduate nursing students and clinical faculty regarding the importance of missed or omitted Parkinson's disease medications during care transitions. To improve quality and safety among this vulnerable population, an innovative, simulated unfolding case study focusing on incomplete medication reconciliation and omission of time-sensitive medications was conducted. Second-degree BSN students (n = 94) and clinical faculty (n = 7) participated in the study. Pretest/posttest results were compared. Findings indicated increased understanding among students and faculty regarding the impact of medication reconciliation and the timely administration of Parkinson's disease medication.


Assuntos
Erros de Medicação/prevenção & controle , Doença de Parkinson/tratamento farmacológico , Transferência de Pacientes , Bacharelado em Enfermagem , Docentes de Enfermagem/psicologia , Humanos , Pesquisa em Avaliação de Enfermagem , Estudantes de Enfermagem/psicologia
15.
Expert Opin Pharmacother ; 20(13): 1659-1670, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31150294

RESUMO

Introduction: Parkinson's disease (PD) causes progressive motor symptoms including tremor, rigidity, and bradykinesia, along with non-motor symptoms such as dementia, orthostatic hypotension, and depression. Over time, PD can lead to falls, disability, institutionalization, and caregiver burden. Its treatment is symptomatic and can be associated with high costs. Areas covered: The authors performed a literature search of PubMed, Web of Science, and Cochrane Library Current for English language PD pharmacoeconomic evaluations starting from 1 January 2000. The authors found 26 papers covering treatment of motor symptoms (n = 24), dementia (n = 1), and orthostatic hypotension (n = 1). The scope of literature was limited in that there were few articles overall. Expert opinion: Overall, the authors found a scarcity of primary PD pharmacoeconomic literature in the 21st Century. Given the myriad of PD motor and non-motor treatments, only 24 papers evaluating motor treatments and two papers evaluating non-motor treatments met our search criteria. More studies are clearly needed to better define the pharmacoeconomics of PD therapeutics.


Assuntos
Antiparkinsonianos/uso terapêutico , Farmacoeconomia , Doença de Parkinson/tratamento farmacológico , Antiparkinsonianos/economia , Humanos , Doença de Parkinson/economia
16.
Medicine (Baltimore) ; 98(24): e16082, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31192971

RESUMO

BACKGROUND: In recent years, L-3-n-butylphthalide (L-NBP) has been used for Parkinson disease dementia (PDD) to attenuate cognitive impairments in China. Therefore, we selected published and qualified clinical trials to conduct a systematic review and meta-analysis with the aim of assessing the effectiveness and safety of L-NBP in the treatment of PDD. OBJECTIVE: This systematic review and meta-analysis aimed to assess the effectiveness and safety of L-NBP in the treatment of PDD. METHODS: We searched PubMed, EMBASE, China National Knowledge Infrastructure, Chinese Scientific Journal Database (VIP database), and Wan-Fang Database to collect eligible articles. We calculated pooled estimates of odds ratios or the standard mean deviation with 95% confidence intervals. RESULTS: Eight randomized controlled trials were included in our meta-analysis. Our meta-analysis showed that L-NBP combined with Western medicine (WM) had a better effect on improving cognitive dysfunction, the total effective rate, symptoms of Parkinson disease (PD), and activities of daily living function than WM alone. Regarding safety, no serious adverse events were observed in the experimental group. CONCLUSION: We found that L-NBP as a complementary therapy may have a positive therapeutic effect for improving cognitive dysfunction, the total effective rate, symptoms of PD, quality of life, and the related serum factors in the treatment of PDD. Furthermore, L-NBP was a safe treatment for PDD. However, the findings of our meta-analysis may be influenced by the low quality of the included studies. We highlight the need to conduct trials with higher methodological quality.


Assuntos
Antiparkinsonianos/administração & dosagem , Benzofuranos/administração & dosagem , Demência/tratamento farmacológico , Nootrópicos/administração & dosagem , Doença de Parkinson/tratamento farmacológico , Antiparkinsonianos/efeitos adversos , Benzofuranos/efeitos adversos , Cápsulas , Demência/etiologia , Humanos , Nootrópicos/efeitos adversos , Doença de Parkinson/psicologia , Ensaios Clínicos Controlados Aleatórios como Assunto
17.
Molecules ; 24(11)2019 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-31185705

RESUMO

Parkinson's disease, a chronic, age related neurodegenerative disorder, is characterized by a progressive loss of nigrostriatal dopaminergic neurons. Several studies have proven that the activation of glial cells, presence of alpha-synuclein aggregates, and oxidative stress, fuels neurodegeneration, and currently there is no definitive treatment for PD. In this study, a rotenone-induced rat model of PD was used to understand the neuroprotective potential of Lycopodium (Lyc), a commonly-used potent herbal medicine. Immunohistochemcial data showed that rotenone injections significantly increased the loss of dopaminergic neurons in the substantia nigra, and decreased the striatal expression of tyrosine hydroxylase. Further, rotenone administration activated microglia and astroglia, which in turn upregulated the expression of α-synuclein, pro-inflammatory, and oxidative stress factors, resulting in PD pathology. However, rotenone-injected rats that were orally treated with lycopodium (50 mg/kg) were protected against dopaminergic neuronal loss by diminishing the expression of matrix metalloproteinase-3 (MMP-3) and MMP-9, as well as reduced activation of microglia and astrocytes. This neuroprotective mechanism not only involves reduction in pro-inflammatory response and α-synuclein expression, but also synergistically enhanced antioxidant defense system by virtue of the drug's multimodal action. These findings suggest that Lyc has the potential to be further developed as a therapeutic candidate for PD.


Assuntos
Encéfalo/patologia , Neurônios Dopaminérgicos/patologia , Inflamação/patologia , Lycopodium/química , Estresse Oxidativo , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/patologia , Extratos Vegetais/uso terapêutico , Animais , Antioxidantes/metabolismo , Catalase/metabolismo , Ciclo-Oxigenase 2/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças , Neurônios Dopaminérgicos/efeitos dos fármacos , Glutationa/metabolismo , Mediadores da Inflamação/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Malondialdeído/metabolismo , Metaloproteinases da Matriz/metabolismo , Microglia/efeitos dos fármacos , Microglia/metabolismo , Degeneração Neural/patologia , Neuroproteção/efeitos dos fármacos , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Nitritos/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Ratos Wistar , Rotenona , Superóxido Dismutase/metabolismo , alfa-Sinucleína/metabolismo
18.
Mar Drugs ; 17(6)2019 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-31146323

RESUMO

Pharmaceutical agents for halting the progression of Parkinson's disease (PD) are lacking. The current available medications only relieve clinical symptoms and may cause severe side effects. Therefore, there is an urgent need for novel drug candidates for PD. In this study, we demonstrated the neuroprotective activity of stellettin B (SB), a compound isolated from marine sponges. We showed that SB could significantly protect SH-SY5Y cells against 6-OHDA-induced cellular damage by inhibiting cell apoptosis and oxidative stress through PI3K/Akt, MAPK, caspase cascade modulation and Nrf2/HO-1 cascade modulation, respectively. In addition, an in vivo study showed that SB reversed 6-OHDA-induced a locomotor deficit in a zebrafish model of PD. The potential for developing SB as a candidate drug for PD treatment is discussed.


Assuntos
Apoptose/efeitos dos fármacos , Heme Oxigenase-1/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Poríferos/química , Triterpenos/farmacologia , Animais , Organismos Aquáticos/química , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Modelos Animais de Doenças , Humanos , Locomoção/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Oxidopamina/toxicidade , Doença de Parkinson/tratamento farmacológico , Triterpenos/química , Triterpenos/isolamento & purificação , Peixe-Zebra
19.
Drugs ; 79(10): 1037-1051, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31161537

RESUMO

Kinase activating missense mutations in leucine-rich repeat kinase 2 (LRRK2) are pathogenically linked to neurodegenerative Parkinson's disease (PD). Over the past decade, substantial effort has been devoted to the development of potent and selective small molecule inhibitors of LRRK2, as well as their preclinical testing across different Parkinson's disease models. This review outlines the genetic and biochemical evidence that pathogenic missense mutations increase LRRK2 kinase activity, which in turn provides the rationale for the development of small molecule inhibitors as potential PD therapeutics. An overview of progress in the development of LRRK2 inhibitors is provided, which in particular indicates that highly selective and potent compounds capable of clinical utility have been developed. We outline evidence from rodent- and human-induced pluripotent stem cell models that support a pathogenic role for LRRK2 kinase activity, and review the substantial experiments aimed at evaluating the safety of LRRK2 inhibitors. We address challenges still to overcome in the translational therapeutic pipeline, including biomarker development and clinical trial strategies, and finally outline the potential utility of LRRK2 inhibitors for other genetic forms of PD and ultimately sporadic PD. Collective evidence supports the ongoing clinical translation of LRRK2 inhibitors as a therapeutic intervention for PD is greatly needed.


Assuntos
Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina/antagonistas & inibidores , Doença de Parkinson/tratamento farmacológico , Inibidores de Proteínas Quinases/química , Animais , Biomarcadores , Linhagem Celular , Regulação da Expressão Gênica , Humanos , Células-Tronco Pluripotentes Induzidas , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina/genética , Terapia de Alvo Molecular/métodos , Mutação , Inibidores de Proteínas Quinases/metabolismo , Roedores
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