scholarly journals Future Treatment of Parkinson’s Disease

1992 ◽  
Vol 19 (S1) ◽  
pp. 160-162
Author(s):  
Joseph King Ching Tsui
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Dopamine Agonists ◽  
Protective Action ◽  
Neuronal Loss ◽  
Methyl Transferase ◽  
Slowing Down ◽  
D1 Agonists ◽  
Long Acting

ABSTRACT:New methods of drug delivery and slowing down the progression of Parkinson’s disease (PD) are the major goals of research. More steady drug levels in the blood are possible by means of controlled-release preparations of levodopa and long-acting dopamine agonists, as well as transcutaneous duodenal tubes and pumps for controlled subcutaneous infusion. Patches containing dopamine agonists absorbed through the skin may be developed. The role of D1 agonists as compared with D2 agonists remains to be elucidated. Agonists on autoreceptors of dopaminergic neurons may potentially reduce excessive stimulation of the intact neurons and this may slow down the rate of neuronal death in PD. Monoamine oxidase-B inhibitors may have a potentially protective action on neurons. Investigations are being carried out to evaluate this claim. Catechol-o-methyl-transferase inhibitors may be helpful in theory. There is also recent interest in inhibitors of excitatory amino acids, which may contribute to neuronal loss in PD.

The VPS35-D620N mutation is associated with Parkinson's disease and can be a target for gene therapy

2021 ◽  
Author(s):  
Moataz Dowaidar
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Metabolic Pathways ◽  
Drug Targets ◽  
Neuronal Loss ◽  
Limited Information ◽  
Tau Pathology ◽  
Therapy Goals ◽  
Axonal Degradation

There is evidence that the VPS35 protein impacts degradation of dopaminergic (DA) neuron lifespan and that the D620N mutation is associated with a kind of Parkinson's disease (PD) mimicking idiopathic PD. The incidence of this mutation and the likely pathogenic effects of additional VPS35 variants is unclear. Other unusual VPS35 mutations may put people at risk for Parkinson's disease, but the level of risk has yet to be determined.Due to the functional and genetic links between VPS35 and other PD-associated genes, rare VPS35 variants may be a key extra component in developing the PD phenotype in people with other mutations with inadequate penetration. Genetic association analysis could remedy this issue in the near future.VPS35-associated PD neuropathology is another significant aspect. Since just one D620N mutant carrier has been studied at autopsy to date, limited information is available about the neuropathological spectrum of PD patients with VPS35 mutations. It is yet unknown if neuronal loss in VPS35-related PD occurs just in SNc or affects other brain areas such as locus coeruleus, cortex, hippocampus and other structures. Neuropathology of VPS35-D620N mice models demonstrated severe tau pathology and axonal degradation, but no evidence of SYN inclusions. It's uncertain if PD individuals with VPS35 mutations have the same features.More study on the role of VPS35 in enhancing DA neuron survival is also needed to better understand the metabolic pathways damaged by VPS35 mutations and identify new therapy goals. The D620N VPS35 KI model, paired with the parkinQ311X mouse model, is one of the first monogenic PD models to recapitulate the fundamental PD feature: DA neuronal breakdown in SNc. These mouse models can be used to identify and assess drug targets. Because the neurodegenerative molecular pathways in many types of Parkinson's disease are so similar, drugs that confer neuroprotection in VPS35 models could be studied in other, more common types of Parkinson's disease.

The role of dopamine agonists in early Parkinson's disease

Neurology ◽  
1997 ◽  
Vol 49 (Issue 1, Supplement 1) ◽  
pp. S34-S48 ◽  
Author(s):  
R. L. Watts
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Dopamine Agonists ◽  
Early Parkinson’S Disease

scholarly journals Cardiac Tyrosine Hydroxylase Activation and Mb-Comt in Dyskinetic Monkeys

2021 ◽  
Author(s):  
Lorena Cuenca-Bermejo ◽  
Pilar Almela ◽  
Pablo Gallo-Soljancic ◽  
José Yuste ◽  
Vicente de Pablos ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Tyrosine Hydroxylase ◽  
Dopaminergic System ◽  
Nigrostriatal Pathway ◽  
Noradrenergic Neurons ◽  
Methyl Transferase ◽  
Mptp Treatment ◽  
The Impact

Abstract The impact of age-associated disorders is increasing as the life expectancy of the population increments. Cardiovascular diseases and neurodegenerative disorders, such as Parkinson’s disease, have the highest social and economic burden and increasing evidence show interrelations between them. Particularly, dysfunction of the cardiovascular nervous system is part of the dysautonomic symptoms of Parkinson’s disease, although more studies are needed to elucidate the role of cardiac function on it. We analyzed the dopaminergic system in the nigrostriatal pathway of Parkinsonian and dyskinetic monkeys and the expression of some key proteins in the metabolism and synthesis of catecholamines in the heart: total and phosphorylated (phospho) tyrosine hydroxylase (TH), and membrane (MB) and soluble (S) isoforms of catechol-O-methyl transferase (COMT). The dopaminergic system was significantly depleted in all MPTP-intoxicated monkeys. MPTP- and MPTP+L-DOPA-treated animals also showed a decrease in total TH expression in both right (RV) and left ventricle (LV). We found a significant increase of phospho-TH in both groups (MPTP and MPTP+L-DOPA) in the LV, while this increase was only observed in MPTP-treated monkeys in the RV. MB-COMT analysis showed a very significant increase of this isoform in the LV of MPTP- and MPTP+L-DOPA-treated animals, with no significant differences in S-COMT levels. These data suggest that MB-COMT is the main isoform implicated in the cardiac noradrenergic changes observed after MPTP treatment, suggesting an increase in NA metabolism. Moreover, the increase of TH activity indicates that cardiac noradrenergic neurons still respond despite MPTP treatment.

scholarly journals A szelektív monoaminoxidáz-B-gátlók helye a Parkinson-kór kezelési stratégiájában a marosvásárhelyi ideggyógyászati klinikák gyakorlatában

2017 ◽  
Vol 158 (51) ◽  
pp. 2023-2028
Author(s):  
József Attila Szász ◽  
Viorelia Constantin ◽  
Péter Alpár Fazakas ◽  
Eszter Blényesi ◽  
Levente Gábor Grieb ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Monoamine Oxidase ◽  
Dopamine Agonists ◽  
Disease Duration ◽  
Monoamine Oxidase Inhibitors ◽  
Monoamine Oxidase B ◽  
Advanced Stages ◽  
Therapeutic Recommendations

Abstract: Introduction: Selective monoamine oxidase B inhibitors have an accurate place in therapeutical strategy of Parkinsons’s disease. In the early stages of the disease, especially in younger patients with milder symptoms, the introduction of levodopa substitution could be efficacious in delaying; in advanced stages they are mainly used to treat motor complications, as an adjunct to levodopa. Aim: The evaluation of therapeutical strategies used in the neurology clinics of Tirgu Mures County Emergency Clinical Hospital in order to define the role of monoamine oxidase B inhibitors. Method: This retrospective study includes all records of patients with Parkinson’s disease hospitalized between 1 January 2003 and 31 December 2016. From the 2194 reports we used data focusing on the therapeutic recommendations. Regarding disease duration, we divided the patients in two groups: less than or equal to 5 years and more than 5 years. Results: From the 1183 patients in first group, 243 received monoamine oxidase inhibitors: 12 as monotherapy, 52 together with dopamine agonists, in 61 cases combined with levodopa. In 118 cases monoamine oxidase inhibitors were combined with levodopa and dopamine agonists. From 582 cases whith Parkinson’s disease for more than 5 years, 195 received monoamine oxidase B inhibitors (selegiline: 10 cases, rasagiline: 185 cases). In 429 cases we did not find accurate data regarding disease duration (selegiline: 5 cases, rasagiline: 93 cases). Conclusion: The use of monoamine oxidase B inhibitors was similar to those found in literature. The treating physicians should utilise more confidently the available therapeutical combinations. Orv Hetil. 2017; 158(51): 2023–2028.

scholarly journals Long-Acting Versus Standard Non-Ergot Dopamine Agonists in Parkinson's Disease: A Meta-Analysis of Randomized Controlled Trials

2014 ◽  
Vol 20 (4) ◽  
pp. 368-376 ◽  
Author(s):  
Chang-Qing Zhou ◽  
Jing-He Lou ◽  
Yu-Ping Zhang ◽  
Ling Zhong ◽  
Ya-Lan Chen ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Randomized Controlled Trials ◽  
Dopamine Agonists ◽  
Meta Analysis ◽  
Controlled Trials ◽  
Randomized Controlled ◽  
Long Acting

Levodopa dosage determines adherence to long-acting dopamine agonists in Parkinson's disease

2012 ◽  
Vol 318 (1-2) ◽  
pp. 90-93 ◽  
Author(s):  
Diego Santos-García ◽  
María Prieto-Formoso ◽  
Raúl de la Fuente-Fernández
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Dopamine Agonists ◽  
Levodopa Dosage ◽  
Long Acting

scholarly journals Venoms as an adjunctive therapy for Parkinson’s disease: where are we now and where are we going?

2021 ◽  
Vol 7 (2) ◽  
pp. FSO642
Author(s):  
Parisa Gazerani
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Dopaminergic Neurons ◽  
Treatment Strategies ◽  
Neuronal Loss ◽  
Diverse Range ◽  
Dopaminergic Neuronal Loss ◽  
New Treatment ◽  
Psychiatric Impairments

Neurodegenerative diseases, including Parkinson’s disease (PD), are increasing in the aging population. Crucially, neurodegeneration of dopaminergic neurons in PD is associated with chronic inflammation and glial activation. Besides this, bradykinesia, resting tremor, rigidity, sensory alteration, and cognitive and psychiatric impairments are also present in PD. Currently, no pharmacologically effective treatment alters the progression of the disease. Discovery and development of new treatment strategies remains a focus for ongoing investigations. For example, one approach is cell therapy to prevent dopaminergic neuronal loss or to slow PD progression. The neuroprotective role of a diverse range of natural products, including venoms from bees, scorpions, snakes and lizards, are also being tested in preclinical PD models and in humans. The main findings from recent studies that have investigated venoms as therapeutic options for PD are summarized in this special report.

Meta-analysis of the efficacy and safety of long-acting non-ergot dopamine agonists in Parkinson’s disease

2014 ◽  
Vol 21 (7) ◽  
pp. 1094-1101 ◽  
Author(s):  
Chang-Qing Zhou ◽  
Jiang-Wei Zhang ◽  
Min Wang ◽  
Guo-Guang Peng
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Dopamine Agonists ◽  
Meta Analysis ◽  
Efficacy And Safety ◽  
Long Acting
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