scholarly journals Historical Perspective: Models of Parkinson’s Disease

2020 ◽  
Vol 21 (7) ◽  
pp. 2464 ◽  
Author(s):  
Shyh Jenn Chia ◽  
Eng-King Tan ◽  
Yin-Xia Chao
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Genetic Manipulation ◽  
Disease Model ◽  
Transgenic Models ◽  
C Elegans ◽  
Wide Range ◽  
Therapeutic Development ◽  
6 Hydroxydopamine

Parkinson’s disease (PD) is the most common movement disorder with motor and nonmotor signs. The current therapeutic regimen for PD is mainly symptomatic as the etio-pathophysiology has not been fully elucidated. A variety of animal models has been generated to study different aspects of the disease for understanding the pathogenesis and therapeutic development. The disease model can be generated through neurotoxin-based or genetic-based approaches in a wide range of animals such as non-human primates (NHP), rodents, zebrafish, Caenorhabditis (C.) elegans, and drosophila. Cellular-based disease model is frequently used because of the ease of manipulation and suitability for large-screen assays. In neurotoxin-induced models, chemicals such as 6-hydroxydopamine (6-OHDA), 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), rotenone, and paraquat are used to recapitulate the disease. Genetic manipulation of PD-related genes, such as α-Synuclein(SNCA), Leucine-rich repeat kinase 2 (LRRK2), Pten-Induced Kinase 1 (PINK1), Parkin(PRKN), and Protein deglycase (DJ-1) Are used in the transgenic models. An emerging model that combines both genetic- and neurotoxin-based methods has been generated to study the role of the immune system in the pathogenesis of PD. Here, we discuss the advantages and limitations of the different PD models and their utility for different research purposes.

scholarly journals Intranasal delivery of mitochondria for treatment of Parkinson’s Disease model rats lesioned with 6-hydroxydopamine

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jui-Chih Chang ◽  
Yi-Chun Chao ◽  
Huei-Shin Chang ◽  
Yu-Ling Wu ◽  
Hui-Ju Chang ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Olfactory Bulb ◽  
Disease Model ◽  
Intranasal Delivery ◽  
The Difference ◽  
And Migration ◽  
6 Hydroxydopamine ◽  
Locomotor Behaviors ◽  
Migratory Stream

AbstractThe feasibility of delivering mitochondria intranasally so as to bypass the blood–brain barrier in treating Parkinson's disease (PD), was evaluated in unilaterally 6-OHDA-lesioned rats. Intranasal infusion of allogeneic mitochondria conjugated with Pep-1 (P-Mito) or unconjugated (Mito) was performed once a week on the ipsilateral sides of lesioned brains for three months. A significant improvement of rotational and locomotor behaviors in PD rats was observed in both mitochondrial groups, compared to sham or Pep-1-only groups. Dopaminergic (DA) neuron survival and recovery > 60% occurred in lesions of the substantia nigra (SN) and striatum in Mito and P-Mito rats. The treatment effect was stronger in the P-Mito group than the Mito group, but the difference was insignificant. This recovery was associated with restoration of mitochondrial function and attenuation of oxidative damage in lesioned SN. Notably, P-Mito suppressed plasma levels of inflammatory cytokines. Mitochondria penetrated the accessory olfactory bulb and doublecortin-positive neurons of the rostral migratory stream (RMS) on the ipsilateral sides of lesions and were expressed in striatal, but not SN DA neurons, of both cerebral hemispheres, evidently via commissural fibers. This study shows promise for intranasal delivery of mitochondria, confirming mitochondrial internalization and migration via RMS neurons in the olfactory bulb for PD therapy.

scholarly journals The Protective Role of Brain CYP2J in Parkinson’s Disease Models

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Yueran Li ◽  
Jinhua Wu ◽  
Xuming Yu ◽  
Shufang Na ◽  
Ke Li ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Brain Regions ◽  
Protective Role ◽  
Neural Cells ◽  
Endogenous Substrates ◽  
6 Hydroxydopamine ◽  
Myd88 Signaling ◽  
Lps Treatment

CYP2J proteins are present in the neural cells of human and rodent brain regions. The aim of this study was to investigate the role of brain CYP2J in Parkinson’s disease. Rats received right unilateral injection with lipopolysaccharide (LPS) or 6-hydroxydopamine (6-OHDA) in the substantia nigra following transfection with or without the CYP2J3 expression vector. Compared with LPS-treated rats, CYP2J3 transfection significantly decreased apomorphine-induced rotation by 57.3% at day 12 and 47.0% at day 21 after LPS treatment; moreover, CYP2J3 transfection attenuated the accumulation of α-synuclein. Compared with the 6-OHDA group, the number of rotations by rats transfected with CYP2J3 decreased by 59.6% at day 12 and 43.5% at day 21 after 6-OHDA treatment. The loss of dopaminergic neurons and the inhibition of the antioxidative system induced by LPS or 6-OHDA were attenuated following CYP2J3 transfection. The TLR4-MyD88 signaling pathway was involved in the downregulation of brain CYP2J induced by LPS, and CYP2J transfection upregulated the expression of Nrf2 via the inhibition of miR-340 in U251 cells. The data suggest that increased levels of CYP2J in the brain can delay the pathological progression of PD initiated by inflammation or neurotoxins. The alteration of the metabolism of the endogenous substrates (e.g., AA) could affect the risk of neurodegenerative disease.

Potential role of protein stabilizers in amelioration of Parkinson's disease and associated effects in transgenic Caenorhabditis elegans model expressing alpha-synuclein

RSC Advances ◽  
2015 ◽  
Vol 5 (95) ◽  
pp. 77706-77715 ◽  
Author(s):  
Supinder Kaur ◽  
Aamir Nazir
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Caenorhabditis Elegans ◽  
Potential Role ◽  
Alpha Synuclein ◽  
C Elegans

Studies employing transgenicC. elegansmodel show that trehalose, a protein stabilizer, alleviates manifestations associated with Parkinson's diseaseviaits inherent activity and through induction of autophagic machinery.

Locomotor Assessment of 6-Hydroxydopamine-induced Adult Zebrafish-based Parkinson's Disease Model

10.3791/63355 ◽  
2021 ◽  
Author(s):  
Naemah Md Hamzah ◽  
Siong Meng Lim ◽  
Yuganthini Vijayanathan ◽  
Fei Tieng Lim ◽  
Abu Bakar Abdul Majeed ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Disease Model ◽  
Adult Zebrafish ◽  
6 Hydroxydopamine

Protective role of chrysin on 6-hydroxydopamine-induced neurodegeneration a mouse model of Parkinson's disease: Involvement of neuroinflammation and neurotrophins

2018 ◽  
Vol 279 ◽  
pp. 111-120 ◽  
Author(s):  
André T.R. Goes ◽  
Cristiano R. Jesse ◽  
Michelle S. Antunes ◽  
Fernando V. Lobo Ladd ◽  
Aliny A.B. Lobo Ladd ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mouse Model ◽  
Protective Role ◽  
6 Hydroxydopamine

Elucidating the Neuroprotective Role of Formulated Camel α-Lactalbumin–Oleic Acid Complex by Curating the SIRT1 Pathway in Parkinson’s Disease Model

2020 ◽  
Vol 11 (24) ◽  
pp. 4416-4425
Author(s):  
Saba Ubaid ◽  
Mohammad Rumman ◽  
Babita Singh ◽  
Mohd. Sohail Akhtar ◽  
Abbas A. Mahdi ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Oleic Acid ◽  
Disease Model ◽  
Acid Complex

scholarly journals The Role of NOX4 in Parkinson’s Disease with Dementia

2019 ◽  
Vol 20 (3) ◽  
pp. 696 ◽  
Author(s):  
Dong-Hee Choi ◽  
In-Ae Choi ◽  
Cheol Lee ◽  
Ji Yun ◽  
Jongmin Lee
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cognitive Impairment ◽  
Alpha Synuclein ◽  
Cognitive Status ◽  
Dopamine Neurons ◽  
Parkinson’S Disease With Dementia ◽  
6 Hydroxydopamine ◽  
Nigrostriatal Dopamine Neurons

The neuropathology of Parkinson’s disease with dementia (PDD) has been reported to involve heterogeneous and various disease mechanisms. Alpha-synuclein (α-syn) and amyloid beta (Aβ) pathology are associated with the cognitive status of PDD, and NADPH oxidase (NOX) is known to affect a variety of cognitive functions. We investigated the effects of NOX on cognitive impairment and on α-syn and Aβ expression and aggregation in PDD. In the 6-hydroxydopamine (6-OHDA)-injected mouse model, cognitive and motor function, and the levels of α-syn, Aβ, and oligomer A11 after inhibition of NOX4 expression in the hippocampal dentate gyrus (DG) were measured by the Morris water maze, novel object recognition, rotation, and rotarod tests, as well as immunoblotting and immunohistochemistry. After 6-OHDA administration, the death of nigrostriatal dopamine neurons and the expression of α-syn and NOX1 in the substantia nigra were increased, and phosphorylated α-syn, Aβ, oligomer A11, and NOX4 were upregulated in the hippocampus. 6-OHDA dose-dependent cognitive impairment was observed, and the increased cognitive impairment, Aβ expression, and oligomer A11 production in 6-OHDA-treated mice were suppressed by NOX4 knockdown in the hippocampal DG. Our results suggest that increased expression of NOX4 in the hippocampal DG in the 6-OHDA-treated mouse induces Aβ expression and oligomer A11 production, thereby reducing cognitive function.

The Neuroprotective Role of MiR-124-3p in a 6-Hydroxydopamine-Induced Cell Model of Parkinson's Disease via the Regulation of ANAX5

2017 ◽  
Vol 119 (1) ◽  
pp. 269-277 ◽  
Author(s):  
Rui-Fang Dong ◽  
Bing Zhang ◽  
Li-Wen Tai ◽  
Hong-Mei Liu ◽  
Fang-Kun Shi ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cell Model ◽  
6 Hydroxydopamine

scholarly journals Therapeutic Effects of Fucoidan in 6-Hydroxydopamine-Lesioned Rat Model of Parkinson's disease: Role of NADPH oxidase-1

2014 ◽  
Vol 20 (12) ◽  
pp. 1036-1044 ◽  
Author(s):  
Fei-Long Zhang ◽  
Yi He ◽  
Yan Zheng ◽  
Wen-Jing Zhang ◽  
Qi Wang ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Nadph Oxidase ◽  
Rat Model ◽  
Therapeutic Effects ◽  
Nadph Oxidase 1 ◽  
6 Hydroxydopamine

scholarly journals EXPERIMENTAL ANIMAL MODELS OF PARKINSON’S DISEASE: AN OVERVIEW

2020 ◽  
pp. 12-17
Author(s):  
MOHD IMRAN ◽  
ANURADHA MISHRA ◽  
AFREEN USMANI ◽  
ASIF EQBAL
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neurodegenerative Disorder ◽  
Current Treatment ◽  
Review Article ◽  
Transgenic Models ◽  
Slowing Down ◽  
Gradual Loss ◽  
Gait Dysfunction ◽  
6 Hydroxydopamine

Parkinson’s disease (PD) is the 2nd most common neurodegenerative disorder due to gradual loss of dopaminergic nerves in the substantia nigra in the midbrain which leads to motor symptoms: For instance, gait dysfunction, involuntary tremor, rigidity, and progressive postural instability. PD has no cure and available current treatment is only symptomatic. At present, the main treatment of PD relies on Levodopa that slowing down the disease development to some level but can lead to several side effects. The literature confirms the available models of Parkinsonism that is chemical-induced, that is, by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and 6-hydroxydopamine-induced Parkinsonism furthermore transgenic models linked to monogenic alterations in SNCA, LRRK2, UCH-L1, PRKN, and PINK1 genes. In this review article, we conclude that the presently available neurotoxic models of PD that offer a platform for neuroprotective drug discovery.

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