scholarly journals Comparative study of the neurotrophic effects elicited by VEGF-B and GDNF in preclinical in vivo models of Parkinson’s disease

Neuroscience ◽  
2014 ◽  
Vol 258 ◽  
pp. 385-400 ◽  
Author(s):  
X. Yue ◽  
D.J. Hariri ◽  
B. Caballero ◽  
S. Zhang ◽  
M.J. Bartlett ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Comparative Study ◽  
In Vivo Models

scholarly journals Insulin Resistance Promotes Parkinson’s Disease through Aberrant Expression of α-Synuclein, Mitochondrial Dysfunction, and Deregulation of the Polo-Like Kinase 2 Signaling

Cells ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 740 ◽  
Author(s):  
Chien-Tai Hong ◽  
Kai-Yun Chen ◽  
Weu Wang ◽  
Jing-Yuan Chiu ◽  
Dean Wu ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mitochondrial Dysfunction ◽  
Ex Vivo ◽  
Proteinase K ◽  
Ros Production ◽  
Aberrant Expression ◽  
In Vivo Models

Background: Insulin resistance (IR), considered a hallmark of diabetes at the cellular level, is implicated in pre-diabetes, results in type 2 diabetes, and negatively affects mitochondrial function. Diabetes is increasingly associated with enhanced risk of developing Parkinson’s disease (PD); however, the underlying mechanism remains unclear. This study investigated the probable culpability of IR in the pathogenesis of PD. Methods: Using MitoPark mice in vivo models, diabetes was induced by a high-fat diet in the in vivo models, and IR was induced by protracted pulse-stimulation with 100 nM insulin treatment of neuronal cells, in vitro to determine the molecular mechanism(s) underlying altered cellular functions in PD, including mitochondrial dysfunction and α-synuclein (SNCA) aberrant expression. Findings: We observed increased SNCA expression in the dopaminergic (DA) neurons of both the wild-type and diabetic MitoPark mice, coupled with enhanced degeneration of DA neurons in the diabetic MitoPark mice. Ex vivo, in differentiated human DA neurons, IR was associated with increased SNCA and reactive oxygen species (ROS) levels, as well as mitochondrial depolarization. Moreover, we demonstrated concomitant hyperactivation of polo-like kinase-2 (PLK2), and upregulated p-SNCA (Ser129) and proteinase K-resistant SNCA proteins level in IR SH-SY5Y cells, however the inhibition of PLK2 reversed IR-related increases in phosphorylated and total SNCA. Similarly, the overexpression of peroxisome proliferator-activated receptor-γ coactivator 1-alpha (PGC)-1α suppressed ROS production, repressed PLK2 hyperactivity, and resulted in downregulation of total and Ser129-phosphorylated SNCA in the IR SH-SY5Y cells. Conclusions: These findings demonstrate that IR-associated diabetes promotes the development and progression of PD through PLK2-mediated mitochondrial dysfunction, upregulated ROS production, and enhanced SNCA signaling, suggesting the therapeutic targetability of PLK2 and/or SNCA as potential novel disease-modifying strategies in patients with PD.

Potential Mechanism of Venous System for Leukoaraiosis: From post-mortem to in vivo Research

2019 ◽  
Vol 19 (3-4) ◽  
pp. 101-108
Author(s):  
Di Nan ◽  
Yingying Cheng ◽  
Liangshu Feng ◽  
Mingming Zhao ◽  
Di Ma ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Small Vessel Disease ◽  
Venous System ◽  
Cerebral Hypoperfusion ◽  
Periventricular White Matter ◽  
Post Mortem ◽  
In Vivo Evaluation ◽  
In Vivo Models

Background: Leukoaraiosis (LA), widely accepted as a feature of cerebral small vessel disease, significantly increases the incidence of stroke, dementia, and death. Cerebral small artery disease has been considered as one of the main causes of LA. However, since the term “venous collagenosis” (VC) was proposed in an atrophy research in 1995, there have been pathological and neuroimaging studies proving the association between the venous system and LA in aging, Alz­heimer’s disease (AD), and Parkinson’s disease. Summary: Autopsy studies confirmed that thickening of the lumen wall in venules, which results from the deposition of collagen I and III, leading to vessel stenosis or occlusion, is closely associated with LA. Susceptibility-weighted imaging research revealed a controversial association of deep medullary veins and LA in vivo, regarding which there are no standard criteria currently. Nevertheless, retinal venous changes had been reported to increase the risk of LA development, providing a novel way for in vivo evaluation. As for the internal jugular vein, jugular venous reflux could double the LA score in aging and modulate circulation of cerebral spinal fluids. Key Messages: Disruption of the venous system was notably associated with LA in aging, AD, and Parkinson’s disease post-mortem and in in vivo models. The venous pathological changes may induce cerebral hypoperfusion, drainage system disruption, and vasogenic oedema in the veins around the periventricular white matter. The clarification of VC in LA may provide an early prevention and early treatment strategy for LA patients.

Protective effects of SUN N8075, a novel agent with antioxidant properties, in in vitro and in vivo models of Parkinson's disease

2008 ◽  
Vol 1214 ◽  
pp. 169-176 ◽  
Author(s):  
A. Oyagi ◽  
Y. Oida ◽  
H. Hara ◽  
H. Izuta ◽  
M. Shimazawa ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Antioxidant Properties ◽  
Protective Effects ◽  
In Vivo Models ◽  
Novel Agent

scholarly journals DOPAL initiates αSynuclein-mediated impaired proteostasis in neuronal projections leading to enhanced vulnerability in Parkinson's disease.

2021 ◽  
Author(s):  
Anna Masato ◽  
Nicoletta Plotegher ◽  
Andrea Thor ◽  
Stephen Adams ◽  
Michele Sandre ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Protein Quality ◽  
Motor Impairment ◽  
Experimental Models ◽  
Early Event ◽  
In Vivo Models ◽  
Nigrostriatal Neuron ◽  
Presynaptic Protein

Dopamine dyshomeostasis has been acknowledged to be among the determinants of nigrostriatal neuron degeneration in Parkinson's disease (PD). Several studies in experimental models and postmortem PD patients underlined increasing levels of the aldehydic dopamine metabolite 3,4-dihydroxyphenylacetaldehyde (DOPAL), which is highly reactive towards proteins. DOPAL has been shown to covalently modify the presynaptic protein αSynuclein (αSyn), whose misfolding and aggregation represent a major trait of PD pathology, triggering αSyn oligomerization in dopaminergic neurons. Here, we demonstrated that DOPAL elicits αSyn neuronal accumulation and hampers αSyn clearance at synapses and the soma. By combining cellular and in vivo models, we provided evidence that DOPAL-induced αSyn buildup lessens neuronal resilience, compromises synaptic integrity, and overwhelms protein quality control pathways, specifically at neuronal projections. The resulting progressive decline of neuronal homeostasis leads to dopaminergic neuron loss and motor impairment, corroborating the αSyn-DOPAL interplay as an early event in PD neurodegeneration.

scholarly journals The Neuroprotective Effects of Cannabis-Derived Phytocannabinoids and Resveratrol in Parkinson’s Disease: A Systematic Literature Review of Pre-Clinical Studies

2021 ◽  
Vol 11 (12) ◽  
pp. 1573
Author(s):  
Samay Prakash ◽  
Wayne G. Carter
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Unmet Need ◽  
Neuroprotective Agents ◽  
Eligibility Criteria ◽  
Neuroprotective Effects ◽  
In Vivo Models ◽  
Anti Inflammatory ◽  
Nigral Degeneration

Currently, there are no pharmacological treatments able to reverse nigral degeneration in Parkinson’s disease (PD), hence the unmet need for the provision of neuroprotective agents. Cannabis-derived phytocannabinoids (CDCs) and resveratrol (RSV) may be useful neuroprotective agents for PD due to their anti-oxidative and anti-inflammatory properties. To evaluate this, we undertook a systematic review of the scientific literature to assess the neuroprotective effects of CDCs and RSV treatments in pre-clinical in vivo animal models of PD. The literature databases MEDLINE, EMBASE, PsychINFO, PubMed, and Web of Science core collection were systematically searched to cover relevant studies. A total of 1034 publications were analyzed, of which 18 met the eligibility criteria for this review. Collectively, the majority of PD rodent studies demonstrated that treatment with CDCs or RSV produced a significant improvement in motor function and mitigated the loss of dopaminergic neurons. Biochemical analysis of rodent brain tissue suggested that neuroprotection was mediated by anti-oxidative, anti-inflammatory, and anti-apoptotic mechanisms. This review highlights the neuroprotective potential of CDCs and RSV for in vivo models of PD and therefore suggests their potential translation to human clinical trials to either ameliorate PD progression and/or be implemented as a prophylactic means to reduce the risk of development of PD.

3.235 ISOTHIOCYANATES PROTECT AGAINST DOPAMINERGIC CELL DEATH IN IN VITRO AND IN VIVO MODELS OF PARKINSON'S DISEASE

2012 ◽  
Vol 18 ◽  
pp. S212
Author(s):  
F. Morroni ◽  
P. Hrelia ◽  
C. Bolondi ◽  
G. Cantelli-Forti ◽  
A. Tarozzi
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cell Death ◽  
In Vivo Models ◽  
Dopaminergic Cell

scholarly journals Comparison of Adaptive Neuroprotective Mechanisms of Sulforaphane and its Interconversion Product Erucin in in Vitro and in Vivo Models of Parkinson’s Disease

2018 ◽  
Vol 66 (4) ◽  
pp. 856-865 ◽  
Author(s):  
Fabiana Morroni ◽  
Giulia Sita ◽  
Alice Djemil ◽  
Massimo D’Amico ◽  
Letizia Pruccoli ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
In Vivo Models
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