A Randomized, Placebo-Controlled, Double-Blind Study to Assess the Efficacy and Safety of LYC-30937-EC in Subjects With Moderate Chronic Plaque-Type Psoriasis

The objective of this Phase 2 trial is to determine the efficacy and safety of LYC-30937-EC in patients with moderate plaque-type psoriasis.

开始日期2016-12-05

申办/合作机构

Lycera Corp.

NCT02764229 / Terminated临床2期

A Multicenter Open-label Extension Study to Assess the Safety and Tolerability of LYC-30937-EC in Subjects With Active Ulcerative Colitis

The purpose of this study is to allow subjects completing study LYC-30937-2001 the opportunity to receive LYC-30937-EC 25 mg.

开始日期2016-11-01

申办/合作机构

Lycera Corp.

NCT02762500 / Completed临床2期

A Randomized, Double-Blind, Placebo-Controlled Parallel Group Study to Assess the Efficacy and Safety of Induction Therapy With LYC-30937-EC in Subjects With Active Ulcerative Colitis

The purpose of the study is to evaluate the efficacy and safety of LYC-30937-EC given orally once daily in subjects with active ulcerative colitis (UC) defined as a total Mayo score (TMS) of 4-11 inclusive, with an endoscopic score of ≥ 2 and a rectal bleeding score of ≥ 1 at screening.

开始日期2016-07-01

申办/合作机构

Lycera Corp.

100 项与 F1F0-ATPase 相关的临床结果

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100 项与 F1F0-ATPase 相关的转化医学

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0 项与 F1F0-ATPase 相关的专利（医药）

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项与 F1F0-ATPase 相关的文献（医药）

2024-08-01·Advanced Science

CKB Promotes Mitochondrial ATP Production by Suppressing Permeability Transition Pore

Article

作者: He, Le ; Lu, Shaojuan ; Yan, Qixin ; Liu, Hailiang ; Lin, Jianghua ; Wu, Xinyi ; Chen, Jie ; Shi, Yufeng ; Li, Hui ; Li, Hao

AbstractCreatine kinases are essential for maintaining cellular energy balance by facilitating the reversible transfer of a phosphoryl group from ATP to creatine, however, their role in mitochondrial ATP production remains unknown. This study shows creatine kinases, including CKMT1A, CKMT1B, and CKB, are highly expressed in cells relying on the mitochondrial F1F0 ATP synthase for survival. Interestingly, silencing CKB, but not CKMT1A or CKMT1B, leads to a loss of sensitivity to the inhibition of F1F0 ATP synthase in these cells. Mechanistically, CKB promotes mitochondrial ATP but reduces glycolytic ATP production by suppressing mitochondrial calcium (mCa2+) levels, thereby preventing the activation of mitochondrial permeability transition pore (mPTP) and ensuring efficient mitochondrial ATP generation. Further, CKB achieves this regulation by suppressing mCa2+ levels through the inhibition of AKT activity. Notably, the CKB‐AKT signaling axis boosts mitochondrial ATP production in cancer cells growing in a mouse tumor model. Moreover, this study also uncovers a decline in CKB expression in peripheral blood mononuclear cells with aging, accompanied by an increase in AKT signaling in these cells. These findings thus shed light on a novel signaling pathway involving CKB that directly regulates mitochondrial ATP production, potentially playing a role in both pathological and physiological conditions.

2024-06-01·Diabetes

Glucose Regulation of β-Cell KATP Channels: Is a New Model Needed?

Review

作者: Rutter, Guy A. ; Sweet, Ian R.

The canonical model of glucose-induced increase in insulin secretion involves the metabolism of glucose via glycolysis and the citrate cycle, resulting in increased ATP synthesis by the respiratory chain and the closure of ATP-sensitive K+ (KATP) channels. The resulting plasma membrane depolarization, followed by Ca2+ influx through L-type Ca2+ channels, then induces insulin granule fusion. Merrins and colleagues have recently proposed an alternative model whereby KATP channels are controlled by pyruvate kinase, using glycolytic and mitochondrial phosphoenolpyruvate (PEP) to generate microdomains of high ATP/ADP immediately adjacent to KATP channels. This model presents several challenges. First, how mitochondrially generated PEP, but not ATP produced abundantly by the mitochondrial F1F0-ATP synthase, can gain access to the proposed microdomains is unclear. Second, ATP/ADP fluctuations imaged immediately beneath the plasma membrane closely resemble those in the bulk cytosol. Third, ADP privation of the respiratory chain at high glucose, suggested to drive alternating, phased-locked generation by mitochondria of ATP or PEP, has yet to be directly demonstrated. Finally, the approaches used to explore these questions may be complicated by off-target effects. We suggest instead that Ca2+ changes, well known to affect both ATP generation and consumption, likely drive cytosolic ATP/ADP oscillations that in turn regulate KATP channels and membrane potential. Thus, it remains to be demonstrated that a new model is required to replace the existing, mitochondrial bioenergetics–based model.

2024-01-01·Neural regeneration research

CHCHD2 Thr61Ile mutation impairs F1F0-ATPase assembly in in vitro and in vivo models of Parkinson's disease.

Article

作者: Tang, Yuting ; Kuang, Yaoyun ; Huang, Shuxuan ; Zhang, Zhiling ; Wu, Zhuohua ; Chen, Xiang ; Zhou, Miaomiao ; Zhu, Xiaoqin ; Dai, Wei ; Guo, Wenyuan ; Zhang, Wenlong ; Liu, Hanqun ; Ye, Panghai ; Xu, Pingyi ; Lin, Yuwan ; Qiu, Jiewen ; Peng, Guoyou

Mitochondrial dysfunction is a significant pathological alteration that occurs in Parkinson's disease (PD), and the Thr61Ile (T61I) mutation in coiled-coil helix coiled-coil helix domain containing 2 (CHCHD2), a crucial mitochondrial protein, has been reported to cause Parkinson's disease. F1F0-ATPase participates in the synthesis of cellular adenosine triphosphate (ATP) and plays a central role in mitochondrial energy metabolism. However, the specific roles of wild-type (WT) CHCHD2 and T61I-mutant CHCHD2 in regulating F1F0-ATPase activity in Parkinson's disease, as well as whether CHCHD2 or CHCHD2 T61I affects mitochondrial function through regulating F1F0-ATPase activity, remain unclear. Therefore, in this study, we expressed WT CHCHD2 and T61I-mutant CHCHD2 in an MPP⁺-induced SH-SY5Y cell model of PD. We found that CHCHD2 protected mitochondria from developing MPP⁺-induced dysfunction. Under normal conditions, overexpression of WT CHCHD2 promoted F1F0-ATPase assembly, while T61I-mutant CHCHD2 appeared to have lost the ability to regulate F1F0-ATPase assembly. In addition, mass spectrometry and immunoprecipitation showed that there was an interaction between CHCHD2 and F1F0-ATPase. Three weeks after transfection with AAV-CHCHD2 T61I, we intraperitoneally injected 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine into mice to establish an animal model of chronic Parkinson's disease and found that exogenous expression of the mutant protein worsened the behavioral deficits and dopaminergic neurodegeneration seen in this model. These findings suggest that WT CHCHD2 can alleviate mitochondrial dysfunction in PD by maintaining F1F0-ATPase structure and function.