Advancement in the modelling and therapeutics of Parkinson’s disease

Nand, Sachchida; Singh, Payal

doi:10.1016/j.jchemneu.2020.101752

Cited by 131 publications

(80 citation statements)

References 242 publications

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“…Toxin‐based models should rarely if ever be employed to study neuroprotection or disease‐modifying therapies. For example, the MPTP‐treated mouse provides too much endogenous dopaminergic substrate and is prone to false positives for disease‐modifying experimental therapeutic strategies 20 . Further dependent on the injection scheme, MPTP only works in mice and monkeys, not at all in rats, and treated monkeys can be prone to spontaneous recovery, 21 often causing misinterpretation of data and a statistical difficulty in separating experimental and control groups from one another.…”

Section: α‐Synucleinopathies: the Use Of Toxin And α‐Synuclein‐based mentioning

confidence: 99%

“…For example, the MPTP-treated mouse provides too much endogenous dopaminergic substrate and is prone to false positives for disease-modifying experimental therapeutic strategies. 20 Further dependent on the injection scheme, MPTP only works in mice and monkeys, not at all in rats, and treated monkeys can be prone to spontaneous recovery, 21 often causing misinterpretation of data and a statistical difficulty in separating experimental and control groups from one another. PD does not spontaneously recover, and thus the mechanisms of functional improvement seen in these animal models may be irrelevant for therapies to be tested in human PD.…”

Section: ---------------------------------------------------------mentioning

confidence: 99%

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Inflammation in Experimental Models of α‐Synucleinopathies

et al. 2020

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Neuroinflammation has long been associated with central nervous system pathology in α‐synucleinopathy disorders including Parkinson's disease and multiple system atrophy. In the past decade, research‐focused efforts in preclinical and experimental models have rallied around this idea, and considerable effort has been made to delineate critical neuroinflammatory processes. In this article, we discuss challenges in preclinical research, notably the use of animal models to recapitulate and dissect disease phenotypes as well as the need for more sensitive, reliable radiotracers to detect on‐target efficacy of immunomodulatory treatments in both human Parkinson's disease as well as preclinical models. © 2020 International Parkinson and Movement Disorder Society

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Section: α‐Synucleinopathies: the Use Of Toxin And α‐Synuclein‐based mentioning

confidence: 99%

Section: ---------------------------------------------------------mentioning

confidence: 99%

Inflammation in Experimental Models of α‐Synucleinopathies

et al. 2020

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“…To model PD in experimental animals toxins, mechanical lesions, genetic manipulations, and α-synuclein preformed fibrils are all used [83,84]. None of available models represents all PD features on a mechanism-related basis.…”

Section: Modeling Pd In Experimental Animals: Emerging Methodsmentioning

confidence: 99%

Can Growth Factors Cure Parkinson’s Disease?

Sidorova

Saarma

2020

Trends in Pharmacological Sciences

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Growth factors (GFs) hold considerable promise for disease modification in neurodegenerative disorders because they can protect and restore degenerating neurons and also enhance their functional activity. However, extensive efforts applied to utilize their therapeutic potential in humans have achieved limited success so far. Multiple clinical trials with GFs were performed in Parkinson's disease (PD) patients, in whom diagnostic symptoms of the disease are caused by advanced degeneration of nigrostriatal dopamine neurons (DNs), but the results of these trials are controversial. This review discusses recent developments in the field of therapeutic use of GFs, problems and obstacles related to this use, suggests the ways to overcome these issues, and alternative approaches that can be used to utilize the potential of GFs in PD management. Neurotrophic Factors and Their Potential in Parkinson's Disease TherapyNeurodegeneration in Parkinson's disease (PD; Box 1) starts from the axons of dopamine (DA) neurons (DNs) in the putamen (Figure 1). When PD is diagnosed there is a 70-80% reduction in the putaminal DA level, approximately 70% decrease in the density of DA axons, but only 30% reduction in the number of DN cell bodies in the substantia nigra pars compacta (SNpc) [1,2]. Therefore, the remaining functional and dystrophic DNs represent an attractive target for supportive and neurorestorative (see Glossary) therapeutic approaches, respectively, which can be provided by growth factors (GFs) including neurotrophic factors (NTFs; Box 2).GFs have been extensively tested in several preclinical PD models (PD models are described in Box 3) and have shown considerable promise for disease modification. Some of them were also trialed in PD patients, but the therapeutic success of such interventions was rather limited. To critically evaluate the results of clinical trials conducted with GFs in PD patients it is important to understand key differences in pharmacology and mode of action of GF treatments compared with conventional small-molecule drugs. Importantly, GFs act in the organism via defined and physiologically relevant molecular pathways in contrast to other agents which are potentially neuroprotective for DN (e.g., an antidiabetic drug exenatide) [3]. Moreover, GFs not only protect, but also restore neurons, promote arborization and sprouting of their neurites, and enhance the functional activity of neurons. These points justify further attempts to translate GFs into drugs for PD treatment. HighlightsGrowth factors (GFs) supporting neuronal survival and increasing their functional activity are promising leads for the development of disease-modifying treatments for neurodegenerative disorders.Clinical use of GFs requires careful planning with regard to dosing, delivery paradigms and equipment, frequency of administration, and the development of patients' stratification criteria.Several alternatives to naturally occurring GFs, such as mutant proteins or small molecules targeting GF receptors, show promise in animal model...

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“…Parkinson's disease (PD) is a common neurodegenerative disease second only to Alzheimer's disease [1,2]. Nowadays, the incidence of PD in my country is rising rapidly with age [3], and it has become one of the main threats to the elderly.…”

Section: Introductionmentioning

confidence: 99%

Momordica Charantia Polysaccharides Attenuates MPP+-Induced Injury in Parkinson’s Disease Mice and Cell Models by Regulating TLR4/MyD88/NF-κB Pathway

Guo

Zhou

Zhang

et al. 2021

International Journal of Polymer Science

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Objective. To investigate the potential role of Momordica charantia polysaccharides (MCPs) in Parkinson’s disease (PD) and reveal the molecular mechanism of its function. Method. 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 1-methyl-4-phenylpyridinium (1-methyl-4-phenylpyridinium, MPP+) were used to establish PD mice and cell models. The mice and cells were divided into 4 groups: Control group, Control+MCPs group, PD group, and PD+MCPs group. Pole climbing experiment and Rotarod experiment were used to observe the coordination ability of mice. High-performance liquid chromatography and enzyme-linked immunosorbent assay (ELISA) were used to determine neurotransmitters and metabolites, inflammatory factors TNF-α and IL-1β, oxidative stress-related markers SOD, MDA, and GSH in striatum tissues. Western blot was used to determine the protein levels of tyrosine hydroxylase (TH), oxidative stress-related protein Cytochrome C (Cytochrome C), and apoptosis-related proteins Bcl-2, Bax, and cleaved Caspase-3 in tissues and cells. Moreover, flow cytometry, PI staining, and fluorescence were used to observe cell apoptosis. Finally, the activation effect of MCPs on TLR4/MyD88/NF-κB signaling pathway was observed and verified. Results. Compared with the Control group, MPTP treatment can induce brain damage in mice (all P < 0.05 ), change the metabolic state of neurotransmitters (all P < 0.05 ), induce inflammation (all P < 0.05 ), and induce apoptosis and the occurrence of oxidation reaction (all P < 0.05 ); however, MCPs treatment can significantly reverse the above changes (all P < 0.05 ). In cell models, studies have found that MCPs can play a protective role by regulating the activation state of TLR4/MyD88/NF-κB pathway. Conclusion. This study found that the application of MCPs therapy can play anti-inflammatory, antioxidative stress, and antiapoptotic effects in PD by regulating the activation of the TLR4/MyD88/NF-κB pathway.

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Advancement in the modelling and therapeutics of Parkinson’s disease

Cited by 131 publications

References 242 publications

Inflammation in Experimental Models of α‐Synucleinopathies

Inflammation in Experimental Models of α‐Synucleinopathies

Can Growth Factors Cure Parkinson’s Disease?

Momordica Charantia Polysaccharides Attenuates MPP+-Induced Injury in Parkinson’s Disease Mice and Cell Models by Regulating TLR4/MyD88/NF-κB Pathway

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