Fig. 1

NURR1 roles in the metabolism of α-synuclein, lipids, glucose, and mitochondria. Sharp arrows (positive regulation), rounded arrows (negative regulation) (A) α-Synuclein, and NURR1 have a detrimental impact on each other. α-Synuclein promotes inflammatory mediators and free radicals, and they, in turn, exacerbate α-synuclein accumulation, creating a vicious cycle, and NURR1 could interrupt this vicious cycle. B NURR1 activates GLUT4 transcription and induces genes involved in glucose and glycogen metabolism; Simultaneously, NURR1 expression could be inhibited by high glucose. Fasting and glucagon treatment induce Nurr1 expression (C) NURR1 in DAergic neurons positively regulates many nuclear-encoded mitochondrial genes and protects cells against the mitochondrial membrane and reactive oxygen species (D) Activating NURR1 promotes the oxidation of FAs, also up-regulates FABP5 expression. Furthermore, unsaturated FAs activate transcriptional function of NURR1. NURR1 expression and nuclear translocation are increased in response to a lipotoxic insult of palmitate. Abbreviations: NURR1: Nuclear receptor-related factor 1; FABP5: Fatty acid-binding protein 5; GLUT: Glucose transporter; Pygm: Phosphorylase glycogen muscle; Phka1: Phosphorylase kinase α 1; Pgam: Phosphoglycerate mutase 2; PGE2: Prostaglandin E2; NFR1,2: Nuclear respiratory factors 1 and 2; PGC-1α: Peroxisome proliferator-activated receptor-gamma coactivator1-alpha