PRECLINICAL MODELS | CNS | PD
Parkinson's disease
IN VITRO models
Primary culture of mesencephalic neurons (dopaminergic neurons):
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Mitochondrial toxins (6-OHDA, MPP+, rotenone) (Callizot et al., 2019)
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Lysosomal toxin (CBE)
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α-synuclein / protofibrils (neurotoxicity)
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Combined toxicity of α-synuclein protofibrils and chronic lysosomal impairment (CBE)
Primary culture of mesencephalic neurons with microglial cells:
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α-synuclein oligomers / protofibrils (neuroinflammation)
Genetic model with point mutation (Crispr/Cas9) in SH-SY5Y cells:
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SH-SY5Y expressing mutated GBAL444P
IN VIVO models
Intra-nigral injection of alpha-synuclein fibrils and lysosomal impairment in aged mice.
Combines the toxicity of alpha-synuclein fibrils and chronic inhibition of GBA, a lysosomal protein, in aged mice.
Our model mimics the main pathologies of PD: loss of dopaminergic neurons in the substancia nigra, neuroinflammation, deficit in motor coordination and synucleinopathy.
Model validated with compounds in clinical trials.