Last update 01 Nov 2024

ERRα

Last update 01 Nov 2024

Basic Info

Synonyms

ERR-alpha, ERR1, ERRa

+ [9]

Introduction

Binds to an ERR-alpha response element (ERRE) containing a single consensus half-site, 5'-TNAAGGTCA-3'. Can bind to the medium-chain acyl coenzyme A dehydrogenase (MCAD) response element NRRE-1 and may act as an important regulator of MCAD promoter. Binds to the C1 region of the lactoferrin gene promoter. Requires dimerization and the coactivator, PGC-1A, for full activity. The ERRalpha/PGC1alpha complex is a regulator of energy metabolism. Induces the expression of PERM1 in the skeletal muscle.

Drugs associated with ERRα

XCT-790

Target

ERRα

Mechanism

ERRα antagonists

Active Org.

Chungnam National University College of Medicine [+2]

Originator Org.

San Francisco Conservatory of Music [+1]

Active Indication

Acute Myeloid Leukemia [+3]

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

DS20362725

Target

ERRα

Mechanism

ERRα agonists

Active Org.

Daiichi Sankyo Co., Ltd.

Originator Org.

Daiichi Sankyo, Inc.

Active Indication-

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

DS45500853

Target

ERRα

Mechanism

ERRα agonists

Active Org.

Daiichi Sankyo Co., Ltd.

Originator Org.

Daiichi Sankyo Co., Ltd.

Active Indication-

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with ERRα

100 Translational Medicine associated with ERRα

0 Patents (Medical) associated with ERRα

2,042

Literatures (Medical) associated with ERRα

31 Dec 2024·Journal of the International Society of Sports Nutrition

Oral post-exercise garlic extract supplementation enhances glycogen replenishment but does not up-regulate mitochondria biogenesis mRNA expression in human-exercised skeletal muscle

Article

Author: Tsai, Tsen-Wei ; Bernard, Jeffrey R ; Chang, Chia-Chen ; Tsao, Jung-Piao ; Liao, Su-Fen ; Cheng, I-Shiung

PURPOSEGarlic extract (GA) is purported to enhance antioxidant and anti-inflammatory activity and glucose regulation in humans. The present study investigated the effects of post-exercise GA supplementation on GLUT4 expression, glycogen replenishment, and the transcript factors involved with mitochondrial biosynthesis in exercised human skeletal muscle.METHODSThe single-blinded crossover counterbalanced study was completed by 12 participants. Participants were randomly divided into either GA (2000 mg of GA) or placebo trials immediately after completing a single bout of cycling exercise at 75% Maximal oxygen uptake (VO_2max) for 60 minutes. Participants consumed either GA (2000 mg) or placebo capsules with a high glycemic index carbohydrate meal (2 g carb/body weight) immediately after exercise. Muscle samples were collected at 0-h and 3-h post-exercise. Muscle samples were used to measure glycogen levels, GLUT4 protein expression, as well as transcription factors for glucose uptake, and mitochondria biogenesis. Plasma glucose, insulin, glycerol, non-esterified fatty acid (NEFA) concentrations, and respiratory exchange ratio (RER) were also analyzed during the post-exercise recovery periods.RESULTSSkeletal muscle glycogen replenishment was significantly elevated during the 3-h recovery period for GA concurrent with no difference in GLUT4 protein expression between the garlic and placebo trials. PGC1-α gene expression was up-regulated for both GA and placebo after exercise (p < 0.05). Transcript factors corresponding to muscle mitochondrial biosynthesis were significantly enhanced under acute garlic supplementation as demonstrated by TFAM and FIS1. However, the gene expression of SIRT1, ERRα, NFR1, NFR2, MFN1, MFN2, OPA1, Beclin-1, DRP1 were not enhanced, nor were there any improvements in GLUT4 expression, following post-exercise garlic supplementation.CONCLUSIONAcute post-exercise garlic supplementation may improve the replenishment of muscle glycogen, but this appears to be unrelated to the gene expression for glucose uptake and mitochondrial biosynthesis in exercised human skeletal muscle.

01 Dec 2024·Neuropharmacology

The PGC-1α/ERRα/ULK1 pathway contributes to Perioperative neurocognitive disorders by inducing mitochondrial dysfunction and activating NLRP3 inflammasome in aged mice

Article

Author: Wu, Cui-Cui ; Tian, Xue-Bi ; Zhang, Guang-Xiong ; Ge, Meng-Meng ; Zhang, Wen ; Yuan, Xiao-Man ; Gao, Feng ; Zhao, Feng-Tian ; Han, Si-Yi ; Tian, Yu-Ke ; Zhang, Xiao-Yu

Perioperative neurocognitive disorders (PND) are intractable, indistinct, and considerably diminish the postoperative quality of life of patients. It has been proved that Peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) was involved in neurodegenerative diseases by regulating mitochondrial biogenesis. The underlying mechanisms of PGC-1α and Nod-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome in PND are not well understood. In this study, we constructed a model of laparotomy in aged mice, and then examined the cognition changes with novel object recognition tests and fear condition tests. The protein levels of PGC-1α and NLRP3 in the hippocampus were detect after surgery. Our results showed that NLRP3 and downstream PI3K/AKT pathway expressions were augmented in the hippocampus after surgery, whereas, the expressions of PGC-1α/estrogen-related receptor α (ERRα)/Unc-51-like autophagy activating kinase 1 (ULK1) pathway were diminished after surgery. In addition, we found that NLRP3 was mainly co-localized with neurons in the hippocampus, and synaptic-related proteins were reduced after surgery. At the same time, transmission electron microscopy (TEM) showed that mitochondria were impaired after surgery. Pharmacological treatment of MCC950, a selective NLRP3 inhibitor, effectively alleviated PND. Activation of PGC-1α with ZLN005 significantly ameliorated PND by enhancing the PGC-1α/ERRα/ULK1 signaling pathway, and further suppressing NLRP3 activation. As a result, we conclude that suppression of the PGC-1α/ERRα/ULK1 signaling pathway is the primary mechanism of PND which caused mitochondrial dysfunction, and activated NLRP3 inflammasome and downstream PI3K/AKT pathway, eventually improved cognitive dysfunction.

01 Dec 2024·European Journal of Medicinal Chemistry

HDAC8 as a target in drug discovery: Function, structure and design

Review

Author: Peng, Jie ; Niu, Haoqian ; Wu, Jingde ; Zhang, Xinbo ; Hao, Huabei ; Liu, Hongyan ; Liu, Xinyu ; Zhao, Qianlong ; Xue, Haoyu ; Liu, Wenjia ; Liu, Jingqian

Histone deacetylases (HDACs) have emerged as prominent therapeutic targets in drug discovery. Among the members of the HDAC family, HDAC8 exhibits distinct structural and physiological features from other members of the class Ⅰ HDACs. In addition to histones, numerous non-histone substrates such as structural maintenance of chromosomes 3 (SMC3), p53, estrogen-related receptor alpha (ERRα), etc., have been identified for HDAC8, suggesting the involvement of HDAC8 in diverse biological processes. Studies have demonstrated that HDAC8 plays essential roles in certain disease development, e.g., acute myeloid leukemia (AML), neuroblastoma, and X-Linked disorders. Despite several HDAC8 inhibitors have been discovered, only one compound has progressed to clinical studies. Recently, novel strategies targeting HDAC8 have emerged, including identifying innovative zinc-chelating groups (ZBG), developing multi-target drugs, and HDAC8 PROTACs. This review aims to summarize recent progress in developing new HDAC8 inhibitors that incorporate novel strategies and provide an overview of the clinical improvements associated with HDAC8 inhibitors.

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ERRα

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