GSE109228 Necroptosis inhibition protects from dopaminergic neuronal cell death in OPA1 mutant Parkinson ’s disease patient neurons and MPTP treated mice

Contributors : Vania Broccoli ; Angelo Iannielli ; Luca Massimino ; Simone BidoSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensDysfunctions in mitochondria dynamics and metabolism are common pathological processes associated with Parkinson ’s disease (PD). Recently, it was shown that an inherited form of PD and dementia is caused by new mutations in the OPA1 gene, which encodes for a key player of mitochondrial fusion and structure. iPSC-derived neural cells from these patients exhibited severe mitochondrial fragmentation, respirati on impairment, ATP deficits and heightened oxidative stress. Reconstitution of normal levels of OPA1 in PD-derived neural cells normalized mitochondria morphology and function. OPA1 mutated neuronal cultures showed reduced survival in vitro. Intriguingly, selective inhibition of necroptosis effectiv ely rescued this survival deficit. Additionally, dampening necroptosis in MPTP treated mice protected from DA neuronal cell loss. This human iPSC-based model captures both the early pathological events in OPA1 mutant neural cells and the beneficial effects of blocking necroptosis, highlighting this cell death process as a promising therapeutic target for PD.
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Homo sapiens Source Type: research