biostudies-literatureUnknown16(1)Duplan ESeveral studies have shown that Parkinson's disease causative gene products, including α-synuclein (α-syn), display tight links with the tumor suppressor p53. The purpose of this study is to determine the implication of α-syn in glioblastoma development and elucidate how it elicits a tumor suppressor function. We show that the expression of α-syn, a TP53 transcriptional target and a key molecular player in Parkinson's disease, is detected in 1p/19q-codeleted and isocitrate dehydrogenase (IDH)-mutant oligodendroglioma and in IDH-wild-type glioblastoma, while reduced in glioblastoma biopsies, corroborating the link of α-syn expression with a better prognosis among all glioma patients. Accordingly, protein expression is drastically reduced in oligodendrogliomas and glioblastoma biopsies. ThisCell death & disease188https://www.ebi.ac.uk/biostudies/studies/S-EPMC11923286biostudies-literatureα-synuclein expression in glioblastoma restores tumor suppressor function and rescues temozolomide drug resistance.PMC11923286Casimiro MHonnorat JLeroudier NIdbaih ATanaka SMartin LCastel HChecler FDuplan EMalleval CGoiran TBernardin APestell RAlves da Costa Cfalseα-synuclein expression in glioblastoma restores tumor suppressor function and rescues temozolomide drug resistance.Several studies have shown that Parkinson's disease causative gene products, including α-synuclein (α-syn), display tight links with the tumor suppressor p53. The purpose of this study is to determine the implication of α-syn in glioblastoma development and elucidate how it elicits a tumor suppressor function. We show that the expression of α-syn, a TP53 transcriptional target and a key molecular player in Parkinson's disease, is detected in 1p/19q-codeleted and isocitrate dehydrogenase (IDH)-mutant oligodendroglioma and in IDH-wild-type glioblastoma, while reduced in glioblastoma biopsies, corroborating the link of α-syn expression with a better prognosis among all glioma patients. Accordingly, protein expression is drastically reduced in oligodendrogliomas and glioblastoma biopsies. This2025-01-01T00:00:00Z2025 Mar2025-04-05T12:37:06.797Z2025-04-05T12:37:06.797ZS-EPMC119232864010811110.1038/s41419-025-07509-z