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PRECLINICAL MODELS  |  CNS  |  PD

Parkinson's disease

IN VITRO models​

Primary culture of mesencephalic neurons (dopaminergic neurons):

  • Mitochondrial toxins (6-OHDA, MPP+, rotenone) (Callizot et al., 2019)

  • Lysosomal toxin (CBE)

  • α-synuclein / protofibrils  (neurotoxicity)

  • Combined toxicity of α-synuclein protofibrils and chronic lysosomal impairment (CBE)

Primary culture of mesencephalic neurons with microglial cells:

  • α-synuclein oligomers / protofibrils (neuroinflammation)

Genetic model with point mutation (Crispr/Cas9) in SH-SY5Y cells:

  • 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.