PT  - JOURNAL ARTICLE
AU  - Svetlana A. Kholodar
AU  - Geoffrey Lang
AU  - Wilian A. Cortopassi
AU  - Yoshie Iizuka
AU  - Harman S. Brah
AU  - Matthew P. Jacobson
AU  - Pamela M. England
TI  - Analogs of the Dopamine Metabolite 5,6-Dihydroxyindole Bind Directly to and Activate the Nuclear Receptor Nurr1 (NR4A2)
AID  - 10.1101/2021.05.09.442997
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.05.09.442997
4099  - http://biorxiv.org/content/early/2021/05/10/2021.05.09.442997.short
4100  - http://biorxiv.org/content/early/2021/05/10/2021.05.09.442997.full
AB  - The nuclear receptor-related 1 protein, Nurr1, is a transcription factor critical for the development and maintenance of dopamine-producing neurons in the substantia nigra pars compacta, a cell population that progressively loses the ability to make dopamine and degenerates in Parkinson’s disease. Recently, we demonstrated that Nurr1 binds directly to and is regulated by the endogenous dopamine metabolite 5,6-dihydroxyindole (DHI). Unfortunately, DHI is an unstable compound, and thus a poor tool for studying Nurr1 function. Here we report that 5-chloroindole, an unreactive analog of DHI, binds directly to the Nurr1 ligand binding domain with micromolar affinity and stimulates the activity of Nurr1, including the transcription of genes governing the synthesis and packaging of dopamine.Competing Interest StatementThe authors have declared no competing interest.