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Parkinson's Disease Models Service
Introduction to Parkinson's Disease Models
Overview of Parkinson's Disease
James Parkinson revealed a detailed description of six patients with shaking palsy in 1817 and after his death, the mentioned description known as Parkinson's disease (PD), which is now the most common neurodegenerative disorder after Alzheimer's disease. The pathological hallmark of PD is the degeneration of dopaminergic neurons of the substantia nigra pars compacta (SNpc). The loss of this neuronal population results in functional imbalances in the nigrostriatal pathway, leading to lowering the level of dopamine (DA) in the striatum. This leads to motor dysfunction and the development of the classical symptoms of PD. Motor symptoms including resting tremor, bradykinesia, and rigidity of skeletal muscle, postural instability, stooped posture, and freezing of gait are clinical symptoms in PD. Furthermore, non-motor symptoms such as cognitive and behavioral problems, besides sensory impairments are seen in the patients. The prevalence of PD is approximately 0.3 % in the general population in developed countries and affects about 1% of those older than 60 and it is unusual to occur before the age of 50. Notably, men are at higher risk than women.
Fig.1 The dopaminergic neuron and the nigrostriatal pathway.1
Importance of In Vitro Models in PD
Animal models are useful for investigating PD progression as they are amenable to behavioral tests. However, as humans are the only species that develop neurodegenerative disorders, it is necessary to induce dopaminergic damage and/or LB pathology in these models. To date, no model has recreated the full spectrum of PD, which makes it difficult to evaluate molecular mechanisms and translate these findings to humans. In vitro models present a controlled environment that facilitates investigations of molecular and cellular pathophysiological mechanisms of dopaminergic degeneration in PD and the screening of potential therapeutics.
Fig. 2 In vitro models of Parkinson's disease.1
Services at Creative Biolabs
As an industry leading CRO, Creative Biolabs has thrown a great deal of manpower, material, and financial resources into in vitro CNS diseases modeling platform. After years of hard work, our platform has finally been completely optimized and opened to customers around the world. We are now capable of offering a variety of custom ex vivo CNS diseases model services, including Parkinson's disease model.
If you are interested in our custom disease model services, or any other custom CNS diseases modeling services on our websites, please don't hesitate to contact us for more information.
In our service, we generally develop in vitro models that comprehensively represent both the cellular and molecular aspects of Parkinson's disease.
- Generation of Parkinson's Disease Cell Models: Our team utilizes different methods including genetic manipulation techniques (like CRISPR-Cas9 system) or chemical exposure to establish different Parkinson's disease cell models from various cell types such as neurons, glial cells, iPSCs, and immortalized cell lines.
- Biochemical Analysis: We measure oxidative stress, mitochondrial dysfunction, protein aggregation, autophagy markers, and other Parkinson-associated biomarkers using techniques such as western blot, immunocytochemistry, ELISA, and fluorescence microscopy.
- Functional Studies: We evaluate functional parameters of Parkinson's disease in our cellular models including cell viability, neurite outgrowth, synaptic plasticity, electrophysiological properties, dopamine release and uptake.
Our service offers innovative, reliable and comprehensive tools to delve deeper into the study of Parkinson's disease. Our team of experienced scientists is available to provide full support and to work closely with your team, ensuring that our services align with your unique research needs. By rendering this service and related services, we aim to accelerate research and drug discovery in neurodegenerative diseases, including but not limited to:
| Services | Descriptions |
|---|---|
| Blood Brain Barrier Models | For different research purposes, we can provide blood-brain barrier modeling customization services to advance your drug development from early discovery to late preclinical stage. |
| Neurotoxicity Screening | Based on our extensive experience in stem cell and genome editing technologies, we can provide new neurotoxicity screening services for CNS drug discovery. For your specific needs, we can also customize the program. |
| Primary Cell Lines | We offer the development of neuroscience-based primary cell lines and related customized products. |
Published Data
Paula Chlebanowska et al. used iPSC cells derived from peripheral blood mononuclear cells (PBMC) from Parkinson's disease patients to generate midbrain organoids. The pluripotency of iPSC was analyzed using techniques that assess pluripotency markers, alkaline phosphatase expression, and the ability to form teratomas in immunodeficient mice. Differentiation was assessed by analyzing dopaminergic neuron (mDA) signature markers at different developmental stages. They aimed to verify whether iPSCs from patients with idiopathic Parkinson's disease have a significant differentiation potential during midbrain organoid formation.
As shown, iPSCs were generated from PBMCs of healthy volunteers and patients with idiopathic PD. iPSCs differentiated into large multicellular organoid-like structures. Mature organoids showed expression of early and late neuronal markers.
Fig. 3 Expression of early and late neurons markers in organoids derived from healthy volunteer and PD patient.2
Application of In Vitro Models in PD Research
PD is still an incurable disease, with current treatments being palliative and only addressing the symptoms. Hence, to date, there are no disease-modifying therapies that can stop or slow PD progression. This is mainly attributed to the lack of understanding regarding the pathogenic process underlying dopaminergic degeneration. A large amount of research data regarding PD pathophysiological mechanisms have been obtained using in vitro experimental models, which provide evidence and hypotheses about the initial steps of PD pathology.
Examples of discoveries in PD research using in vitro models:
- A-synuclein modulation in DA toxicity.
- The involvement of PINK1, PARKIN, and DJ-1 in mitochondrial dysfunction, regarding mitochondrial fragmentation.
- The neuroprotective role of DJ-1 protein, and how its dysfunction can lead to toxic processes in PD.
- Mutation in LRRK2 gene (e.g., G2019S) increases susceptibility to apoptosis and proteasome stress.
Hence, it is clear that in vitro models are useful for the study of PD pathogenic mechanisms and have a clear and essential place among the battery of models available for use in PD studies.
FAQs
Q: What kind of techniques does the service use to create the models?
A: Our service uses advanced techniques like iPSCs and genetically engineered cell lines to develop the Parkinson's disease in vitro models. These techniques allow us to simulate the disease conditions as closely as possible, thereby providing reliable results.
Q: How to ensure the genetic stability of your iPSC-derived models over time?
A: To ensure genetic stability, we perform regular karyotyping and genomic integrity assessments throughout the differentiation process. We also utilize advanced techniques like whole-genome sequencing and single-cell RNA sequencing to monitor for genetic anomalies. Continuous quality control measures are in place to detect and mitigate any potential genetic drift or instability.
Q: How to ensure the long-term viability and functionality of the neurons in your in vitro models?
A: We optimize culture conditions to support the long-term viability and functionality of neurons in our in vitro models. This includes using specialized media formulations, growth factors, and extracellular matrix components that promote neuronal health and maturation. We also perform regular functional assays, such as electrophysiological recordings and neurotransmitter release measurements, to ensure that the neurons maintain their functionality over time.
Q: Do you offer any collaborative research opportunities or partnerships for developing new models or technologies?
A: Yes, we actively seek collaborative research opportunities and partnerships. We work with academic institutions, pharmaceutical companies, and biotech firms to co-develop new models and technologies. Our collaborations aim to advance the understanding of Parkinson's disease and accelerate the development of effective treatments. We are open to exploring various partnership arrangements, including joint research projects and grant applications.
Scientific Resources
References
- Lopes, F. M., et al. Mimicking Parkinson's Disease in a Dish: Merits and Pitfalls of the Most Commonly used Dopaminergic In Vitro Models. Neuromolecular Med. 2017, 19(2-3): 241-255.
- Chlebanowska, Paula, et al. "Use of 3D organoids as a model to study idiopathic form of Parkinson's disease." International Journal of Molecular Sciences 21.3 (2020): 694.
For Research Use Only. Not For Clinical Use.