References of "Ouzren, Nassima 50022583"
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See detailMtDNA deletions discriminate affected from unaffected LRRK2 mutation carriers
Ouzren, Nassima UL; Delcambre, Sylvie UL; Ghelfi, Jenny UL et al

in Annals of Neurology (2019), 86(2), 324-326

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See detail3D Cultures of Parkinson's Disease‐Specific Dopaminergic Neurons for High Content Phenotyping and Drug Testing
Bolognin, Silvia UL; Fossépré, Marie; Qing, Xiaobing et al

in Advanced Science (2018)

Parkinson's disease (PD)‐specific neurons, grown in standard 2D cultures, typically only display weak endophenotypes. The cultivation of PD patient‐specific neurons, derived from induced pluripotent stem ... [more ▼]

Parkinson's disease (PD)‐specific neurons, grown in standard 2D cultures, typically only display weak endophenotypes. The cultivation of PD patient‐specific neurons, derived from induced pluripotent stem cells carrying the LRRK2‐G2019S mutation, is optimized in 3D microfluidics. The automated image analysis algorithms are implemented to enable pharmacophenomics in disease‐relevant conditions. In contrast to 2D cultures, this 3D approach reveals robust endophenotypes. High‐content imaging data show decreased dopaminergic differentiation and branching complexity, altered mitochondrial morphology, and increased cell death in LRRK2‐G2019S neurons compared to isogenic lines without using stressor agents. Treatment with the LRRK2 inhibitor 2 (Inh2) rescues LRRK2‐G2019S‐dependent dopaminergic phenotypes. Strikingly, a holistic analysis of all studied features shows that the genetic background of the PD patients, and not the LRRK2‐G2019S mutation, constitutes the strongest contribution to the phenotypes. These data support the use of advanced in vitro models for future patient stratification and personalized drug development. [less ▲]

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