Altered p53 and Cell Cycle Regulation in SCZ Neural Progenitors

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The following is a summary of “Patient iPSC-derived neural progenitor cells display aberrant cell cycle control, p53, and DNA damage response protein expression in schizophrenia,” published in the October 2024 issue of Psychiatry by Stahl et al. 

Schizophrenia (SCZ) is a psychiatric disorder linked to early brain development alterations. Despite genomic studies, the underlying protein-level mechanisms remain unclear. 

Researchers conducted a retrospective study to analyze protein-level mechanisms in SCZ, B a disorder linked to early brain development alterations. 

They examined SCZ-specific protein signatures in iPSC-derived neuronal progenitor cells (NPC) from patients and controls using Western Blotting (DigiWest). 

The results showed that SCZ neural progenitors displayed altered expression and phosphorylation patterns in Wnt and MAPK signaling, protein synthesis, cell cycle regulation, and DNA damage response. SCZ NPCs showed G2/M cell cycle accumulation, reduced differentiation, and elevated p53 expression and phosphorylation, suggesting p53’s role in impaired cell cycle progression and neurodevelopment. 

The study concluded that SCZ NPCs exhibited mechanistic alterations in DNA damage response, cell cycle control, and p53 expression. These findings supported the use of iPSC-based models to better understand SCZ’s early developmental mechanisms. 

Source: bmcpsychiatry.biomedcentral.com/articles/10.1186/s12888-024-06127-x