TY  - JOUR
A1  - Willems, Sabine
A1  - Marschner, Julian
A1  - Kilu, Whitney
A1  - Faudone, Giuseppe
A1  - Busch, Romy
A1  - Duensing-Kropp, Silke
A1  - Heering, Jan Peter
A1  - Merk, Daniel
T1  - Nurr1 modulation mediates neuroprotective effects of statins
T2  - Advanced science
N2  - The ligand-sensing transcription factor Nurr1 emerges as a promising therapeutic target for neurodegenerative pathologies but Nurr1 ligands for functional studies and therapeutic validation are lacking. Here pronounced Nurr1 modulation by statins for which clinically relevant neuroprotective effects are demonstrated, is reported. Several statins directly affect Nurr1 activity in cellular and cell-free settings with low micromolar to sub-micromolar potencies. Simvastatin as example exhibits anti-inflammatory effects in astrocytes, which are abrogated by Nurr1 knockdown. Differential gene expression analysis in native and Nurr1-silenced cells reveals strong proinflammatory effects of Nurr1 knockdown while simvastatin treatment induces several neuroprotective mechanisms via Nurr1 involving changes in inflammatory, metabolic and cell cycle gene expression. Further in vitro evaluation confirms reduced inflammatory response, improved glucose metabolism, and cell cycle inhibition of simvastatin-treated neuronal cells. These findings suggest Nurr1 involvement in the well-documented but mechanistically elusive neuroprotection by statins.
KW  - Alzheimer’s disease
KW  - multiple sclerosis
KW  - NR4A2
KW  - nuclear receptor related-1
KW  - Parkinson’s disease
Y1  - 2022
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/85628
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-856285
SN  - 2198-3844
N1  - Funding: LOEWE for Translational Medicine and Pharmacology (TMP)
N1  - Funding: Innovative Medicines Initiative 2 Joint Undertaking (JU) ; 875510
N1  - Open Access funding enabled and organized by Projekt DEAL.
VL  - 9
IS  - 18, art. 2104640
SP  - 1
EP  - 17
PB  - Wiley-VCH
CY  - Weinheim
ER  -