Parkinson's Disease (PD) In Vitro Modeling Service
Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra, accumulation of α-synuclein aggregates, mitochondrial dysfunction, and neuroinflammation.
Creative Biolabs is committed to advancing PD research and therapeutic development by providing innovative in vitro models. Our state-of-the-art models, including patient-specific iPSC-derived cells, overexpression of wild-type or mutant α-synuclein, and primary cultures, offer a robust platform for scientists to delve into the fundamental mechanisms of PD, screen potential drug candidates, and study the progression of the disease.
Core Pathological Hallmarks & Cellular Targets
PD pathology involves several key mechanisms:
- Prion-like α-synuclein spread: Misfolded α-synuclein proteins can spread from cell to cell, similar to prions. This process may contribute to the progressive nature of PD.
- LRRK2-dependent mitochondrial-lysosomal crosstalk: Mutations in the LRRK2 gene can disrupt the communication between mitochondria and lysosomes, leading to cellular dysfunction.
- Dopaminergic neuron subtype vulnerability: Specific subtypes of dopaminergic neurons, such as those in the substantia nigra, are selectively lost due to high baseline oxidative stress.
Key cellular targets:
- Dopaminergic neurons: These neurons are primarily affected in PD, leading to a significant loss of dopamine production, which is crucial for motor control and coordination.
- Astrocytes: Models for metabolic support, inflammatory responses, and α-synuclein clearance.
- Microglia: Phagocytic clearance of α-synuclein aggregates and secretion of neurotoxic factors.
- Enteric neurons: Gut-brain axis models to study early α-synuclein pathology.
- Peripheral immune cells: CD4+ T cells co-cultured with neurons to mimic PD-specific neuroinflammation.
Advanced Models for PD Research
At Creative Biolabs, we're driving PD research forward with our diverse portfolio of cutting-edge in vitro models.
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iPSC-Derived Models
- Patient-specific iPSCs: Generated from PD patients with SNCA (α-synuclein), LRRK2 G2019S, or PINK mutations.
- Isogenic controls: CRISPR-corrected iPSC lines to isolate disease-specific phenotypes.
- Midbrain organoids: 3D models containing dopaminergic neurons, astrocytes, and microglia to study cell-cell interactions.
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Immortalized Cell Lines
- SH-SY5Y neuroblastoma cells: Overexpression of wild-type or mutant α-synuclein (A53T, E46K) to study aggregation kinetics.
- HEK293T cells: Used for high-throughput screening of LRRK2 kinase inhibitors.
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Primary Rodent Cultures
- Primary midbrain dopaminergic neurons: Acute exposure to mitochondrial toxins (e.g., MPP, MPTP, rotenone) or alpha-synuclein filaments induces selective dopaminergic death.
- Microglia-astrocyte co-cultures: Model neuroinflammatory crosstalk in response to α-synuclein.
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Advanced Bioengineered Platforms
- Microfluidic gut-brain axis models: Compartmentalized systems to study α-synuclein propagation from enteric neurons to midbrain neurons.
- Optogenetic α-synuclein aggregation: Light-inducible systems (e.g., OptoProphet) to spatiotemporally control α-synuclein oligomerization.
Disease-Specific Assays
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α-Synuclein Pathogenicity Metrics
- FRET-based oligomer sensors: GFP-tagged α-synuclein constructs quantify oligomerization in live neurons.
- Proteolytic resistance assay: Proteinase K digestion + Western blot to detect insoluble α-synuclein.
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Dopaminergic Vulnerability Index
- Tyrosine hydroxylase (TH) decay rate: Live-cell imaging of TH-mCherry fluorescence loss post-rotenone exposure.
- Electrophysiological fingerprint: Patch-clamp recordings of autonomous pacemaking activity (1–4 Hz) in A9 neurons.
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LRRK2 Functional Profiling
- Kinase activity ELISA: Phospho-LRRRK2 (Ser935) levels in iPSC-microglia.
- Rab10 phosphorylation: Phos-tag gel electrophoresis to assess LRRK2-driven lysosomal dysfunction.
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Mitochondrial-QC Workflow
- MitoTimer reporter: Red/green fluorescence ratio indicates mitochondrial oxidative damage.
- Lysosomal pH mapping: LysoTracker Red intensity correlates with lysosomal alkalization in LRRK2 models.
Related Services
- Alpha-Synuclein Aggregation Assay
- Microglia Activation Assay
- MPP+ Neuronal Cell Death Assay
- α-Synuclein Degrader Compound Screen Assay
Ready to take your Parkinson's research to the next level? Collaborate with Creative Biolabs and leverage our advanced in vitro models to accelerate your drug discovery efforts. Contact us today to discuss your research needs and explore how our models can contribute to your success.
Reference
- MacMahon Copas, Adina N et al. "The Pathogenesis of Parkinson's Disease: A Complex Interplay Between Astrocytes, Microglia, and T Lymphocytes?." Front Neurol. 2021;12:666737. Distributed under Open Access License CC BY 4.0 without modification.
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