TY  - JOUR
AU  - Jones, Mattson S O
AU  - Lindlar, Silvia
AU  - Ludwig, Johannes
AU  - Waltes, Regina
AU  - Kumar, Afsheen
AU  - V Brauchitsch, Sophie
AU  - Rossi, Andrea
AU  - Ullrich, Evelyn
AU  - Momma, Stefan
AU  - Freitag, Christine M
AU  - Hefendehl, Jasmin K
AU  - Klein, Karl Martin
AU  - Rosenow, Felix
AU  - Haslinger, Denise
AU  - Chiocchetti, Andreas G
TI  - The transcriptomic signature of DEPDC5 KO induced mTOR hyperactivation in human neurons and its response to rapamycin treatment.
JO  - Epilepsia
VL  - nn
SN  - 0013-9580
CY  - Oxford [u.a.]
PB  - Wiley-Blackwell
M1  - DKFZ-2025-01537
SP  - nn
PY  - 2025
N1  - epub
AB  - Mutations of the DEP Domain Containing 5 gene (DEPDC5), a mechanistic Target of Rapamycin (mTOR) inhibitor involved in amino acid sensing, are associated with neurological diseases such as epilepsy and/or autism spectrum disorder (ASD). Loss of DEPDC5 impacts early neuronal development via mTOR hyperactivity. Although, in the mTOR-hyperactivity-associated syndrome tuberous sclerosis, mTOR inhibitors have proven to be beneficial in treating epilepsy, ASD-associated symptoms are ameliorated only partially. Similarly, the mTOR inhibitor rapamycin (RAPA) only partially rescues phenotypes induced by loss of DEPDC5 in animal models, suggesting some pathological mechanisms independent of mTOR.We dissected these mechanisms by identifying the DEPDC5-associated gene networks and how they are targeted by RAPA in an isogenic primary human neural progenitor (phNPC) DEPDC5 knock-out cell model.We confirm that loss of DEPDC5 leads to hyperactivation of mTOR, paralleled by altered expression of mTOR-associated genes. These effects were partially (up to 33
KW  - ASD (Other)
KW  - comorbidities (Other)
KW  - epilepsy (Other)
KW  - human cell model (Other)
KW  - neural progenitor cells (Other)
KW  - transcriptomics (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:40704780
DO  - DOI:10.1111/epi.18549
UR  - https://inrepo02.dkfz.de/record/303118
ER  -