Open AccessOleic acid is an endogenous ligand of TLX/NR2E1 that triggers hippocampal neurogenesis
Author(s) -
Prasanna Kandel,
Fatih Semerci,
Rachana Mishra,
William T. Choi,
Aleksandar Bajić,
Dodge L. Baluya,
Long Ma,
Kevin Chen,
Austin C. Cao,
Tipwarin Phongmekhin,
Nick Matinyan,
Alba Jiménez-Panizo,
Srinivas Chamakuri,
Idris Raji,
Lyra Chang,
Pablo FuentesPrior,
Kevin R. MacKenzie,
Caroline Benn,
Eva EstébanezPerpiñá,
Koen J. T. Venken,
David D. Moore,
Damian W. Young,
Mirjana Maletić-Savatić
Publication year - 2022
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2023784119
Subject(s) - neurogenesis , neural stem cell , biology , stem cell , microbiology and biotechnology , neural development , hippocampal formation , dentate gyrus , neuroscience , genetics , gene
Significance Adult hippocampal neurogenesis underpins learning, memory, and mood but diminishes with age and certain illnesses. The orphan nuclear receptor TLX/NR2E1 regulates neural stem and progenitor cell self-renewal and proliferation, but its orphan status has hindered its utilization as a therapeutic target to modulate adult neurogenesis. Here, we deorphanize TLX and report that oleic acid is an endogenous, metabolic ligand of TLX. These findings open avenues for future therapeutic modulation of TLX to counteract cognitive and mental decline in aging and diseases associated with decreased neurogenesis.