Experimental Models and New, Emerging Therapies for Parkinson Disease

2007 ◽  
pp. 205-231
Author(s):  
Stanley Fahn ◽  
Joseph Jankovic ◽  
Mark Hallett ◽  
Peter Jenner
Keyword(s):  
Parkinson Disease ◽  
Experimental Models ◽  
Emerging Therapies

scholarly journals New and Emerging Therapies for Pulmonary Arterial Hypertension

2019 ◽  
Vol 70 (1) ◽  
pp. 45-59 ◽  
Author(s):  
Edda Spiekerkoetter ◽  
Steven M. Kawut ◽  
Vinicio A. de Jesus Perez
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Right Ventricular Dysfunction ◽  
Experimental Models ◽  
Metabolic Dysfunction ◽  
Alternative Pathways ◽  
Exercise Limitation ◽  
Emerging Therapies ◽  
New Findings ◽  
Pulmonary Arterial

Pulmonary arterial hypertension (PAH) is a pulmonary vasculopathy that causes right ventricular dysfunction and exercise limitation and progresses to death. New findings from translational studies have suggested alternative pathways for treatment. These avenues include sex hormones, genetic abnormalities and DNA damage, elastase inhibition, metabolic dysfunction, cellular therapies, and anti-inflammatory approaches. Both novel and repurposed compounds with rationale from preclinical experimental models and human cells are now in clinical trials in patients with PAH. Findings from these studies will elucidate the pathobiology of PAH and may result in clinically important improvements in outcome.

NGF in experimental models of parkinson disease

1996 ◽  
Vol 28 (1-3) ◽  
pp. 225-228 ◽  
Author(s):  
L. Lorigados ◽  
P. Alvarez ◽  
N. Pavón ◽  
T. Serrano ◽  
L. Blanco ◽  
...  
Keyword(s):  
Parkinson Disease ◽  
Experimental Models

scholarly journals α-Synuclein pathology in Parkinson disease activates homeostatic NRF2 anti-oxidant response

2021 ◽  
Author(s):  
Alberto Delaidelli ◽  
Mette Richner ◽  
Lixiang Jiang ◽  
Amelia van der Laan ◽  
Ida Bergholdt Jul Christiansen ◽  
...  
Keyword(s):  
Nervous System ◽  
Parkinson Disease ◽  
Redox Homeostasis ◽  
Alpha Synuclein ◽  
Experimental Models ◽  
Motor Nucleus ◽  
Related Factor ◽  
Dorsal Motor Nucleus ◽  
Anti Oxidant

Circumstantial evidence points to a pathological role of alpha-synuclein (aSyn; gene symbol SNCA), conferred by aSyn misfolding and aggregation, in Parkinson disease (PD) and related synucleionpathies. Several findings in experimental models implicate perturbations in the tissue homeostatic mechanisms triggered by pathological aSyn accumulation, including impaired redox homeostasis, as significant contributors in the pathogenesis of PD. The nuclear factor erythroid 2-related factor (NRF2) is recognized as the master regulator of cellular anti-oxidant response, both under physiological as well as in pathological conditions. Using immunohistochemical analyses, we show a robust nuclear NRF2 accumulation in post-mortem PD midbrain, detected by NRF2 phosphorylation on serine residue 40 (nuclear active p-NRF2, S40). Curated gene expression analyses of four independent publicly available microarray datasets revealed considerable alterations in NRF2-responsive genes in the disease affected regions in PD, including substantia nigra, dorsal motor nucleus of vagus, locus coeruleus and globus pallidus. To further examine the putative role of pathological aSyn accumulation on nuclear NRF2 response, we employed a transgenic mouse model of synucleionopathy (M83 line, Prnp-SNCA*Ala53Thr), which manifest widespread aSyn pathology (phosphorylated aSyn; S129) in the nervous system following intramuscular inoculation of exogenous fibrillar aSyn. We observed strong immunodetection of nuclear NRF2 in neuronal populations harboring p-aSyn (S129), and found an aberrant anti-oxidant and inflammatory gene response in the affected neuraxis. Taken together, our data support the notion that pathological aSyn accumulation impairs the redox homeostasis in nervous system, and boosting neuronal anti-oxidant response is potentially a promising approach to mitigate neurodegeneration in PD and related diseases.

A Review on Mitochondrial Dysfunction and Oxidative stress due to Complex-Ⅰ in Parkinson Disease

2021 ◽  
pp. 167-170
Author(s):  
V Nuthan Kumar Babu ◽  
Navneet Khurana
Keyword(s):  
Oxidative Stress ◽  
Parkinson Disease ◽  
Mitochondrial Dysfunction ◽  
Neurodegenerative Disorder ◽  
Dimethyl Fumarate ◽  
World Population ◽  
Emerging Therapies ◽  
And Oxidative Stress ◽  
Transplantation Therapy

Parkinson’s disease (PD) is the common physical movement disorder, and it is 2nd most progressive widespread neurodegenerative disorder all over the world, and it is reported that and essential 10 million, over 0.3 % of the total world population. A thoughtful reduction of the neurotransmitter dopamine (DA) in the striatum is the main cause of these motor symptoms, collectively known as parkinsonism. Mitochondria serves as most important organelle in most of the cells and are essential for life and it is also called as heart for all cellular metabolisms. The main and most important role of mitochondria is generation of ATP via oxidative phosphorylation. In this study will study about how complex Ⅰ deficiency effects the mitochondrial and oxidative stress and reactive oxygen species which cause mitochondrial dysfunction and we also study emerging therapies for Parkinson disease with the help of coenzyme Q10 and some genes like FUN-14, FUNDC-1 and dimethyl fumarate or BG-12 in some phases of clinical trials and also by cell transplantation therapy and in future this study helps in finding how this sporadic Parkinson disease occurs in parkinsonism.

scholarly journals Oxidative Modification of Peroxiredoxin Is Associated with Drug-induced Apoptotic Signaling in Experimental Models of Parkinson Disease

2008 ◽  
Vol 283 (15) ◽  
pp. 9986-9998 ◽  
Author(s):  
Young Mook Lee ◽  
Seong H. Park ◽  
Dong-Ik Shin ◽  
Jee-Yeon Hwang ◽  
BoKyung Park ◽  
...  
Keyword(s):  
Parkinson Disease ◽  
Experimental Models ◽  
Oxidative Modification ◽  
Drug Induced ◽  
Apoptotic Signaling

scholarly journals Metformin Repurposing for Parkinson Disease Therapy: Opportunities and Challenges

2021 ◽  
Vol 23 (1) ◽  
pp. 398
Author(s):  
Francesco Agostini ◽  
Anna Masato ◽  
Luigi Bubacco ◽  
Marco Bisaglia
Keyword(s):  
Parkinson Disease ◽  
Neurodegenerative Disorder ◽  
Low Cost ◽  
Epidemiological Studies ◽  
Experimental Models ◽  
Diabetic Patients ◽  
Motor Disabilities ◽  
Mitochondrial Functions ◽  
Disease Therapy ◽  
Disease Modifier

Parkinson disease (PD) is a severe neurodegenerative disorder that affects around 2% of the population over 65 years old. It is characterized by the progressive loss of nigrostriatal dopaminergic neurons, resulting in motor disabilities of the patients. At present, only symptomatic cures are available, without suppressing disease progression. In this frame, the anti-diabetic drug metformin has been investigated as a potential disease modifier for PD, being a low-cost and generally well-tolerated medication, which has been successfully used for decades in the treatment of type 2 diabetes mellitus. Despite the precise mechanisms of action of metformin being not fully elucidated, the drug has been known to influence many cellular pathways that are associated with PD pathology. In this review, we present the evidence in the literature supporting the neuroprotective role of metformin, i.e., autophagy upregulation, degradation of pathological α-synuclein species, and regulation of mitochondrial functions. The epidemiological studies conducted in diabetic patients under metformin therapy aimed at evaluating the correlation between long-term metformin consumption and the risk of developing PD are also discussed. Finally, we provide an interpretation for the controversial results obtained both in experimental models and in clinical studies, thus providing a possible rationale for future investigations for the repositioning of metformin for PD therapy.

scholarly journals Potential role of lactoferrin in early diagnostics and treatment of Parkinson disease

2020 ◽  
Vol 20 (1) ◽  
pp. 37-44
Author(s):  
Alexey V. Sokolov ◽  
Irina V. Miliukhina ◽  
Yury P. Belsky ◽  
Nataly V. Belska ◽  
Vadim B. Vasilyev
Keyword(s):  
Early Diagnosis ◽  
Substantia Nigra ◽  
Parkinson Disease ◽  
Dopaminergic Neurons ◽  
Experimental Models ◽  
Control Group ◽  
Clear Understanding ◽  
Necrosis Factor Alpha ◽  
Positive Effects ◽  
Factor Alpha

Incidence of Parkinson disease progressively grows with increasing age and percentage of elderly people in the global population. Clear understanding of the causes of dopaminergic neurons death in Substantia nigra and Parkinson disease pathogenesis are currently absent, not speaking of an efficient therapy. However, an early diagnosis of dopaminergic neurons degeneration and prescription of dopamine replacement therapy significantly slow down the rate of symptoms progression. An increased concentration of iron in Substantia nigra of Parkinson disease patients has been shown in several studies. In this review we summarized the data concerning a potential significance of lactoferrin, the iron-binding protein of exocrine secretions and neutrophils, for early diagnosis and treatment of Parkinson disease. Salivary and lacrimal lactoferrin levels in Parkinson disease patients were higher than those observed in the control group. Plasma levels of lactoferrin inversely correlated with Parkinson disease severity even after treatment with Levodopa, a dopamine agonist, and with monoaminooxidase inhibitors. Lactoferrin levels in cerebrospinal fluid of Parkinson disease patients negatively correlated with the tumor necrosis factor-alpha concentration. Lactoferrin treatment of rodents with several experimental models of Parkinson disease (induced by rotenone, MPTP) protected neurons and mitigated the symptoms of neurodegeneration. Some contradictions about the positive effects of lactoferrin as a remedy in Parkinson disease animal models and possible participation of lactoferrin in accumulation of iron in neurons are discussed.

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