更新于：2024-11-01

CHKA x CHKB

更新于：2024-11-01

基本信息

关联

项与 CHKA x CHKB 相关的药物

MN58b

靶点

CHKA x CHKB

作用机制

CHKA抑制剂 [+1]

在研机构

Instituto De Investigaciones Biomédicas De Córdoba

原研机构

Instituto De Investigaciones Biomédicas De Córdoba

在研适应症

肿瘤

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 CHKA x CHKB 相关的临床结果

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100 项与 CHKA x CHKB 相关的转化医学

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0 项与 CHKA x CHKB 相关的专利（医药）

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项与 CHKA x CHKB 相关的文献（医药）

2022-08-01·Journal of Lipid Research2区 · 生物学

Choline kinase inhibition promotes ER-phagy

2区 · 生物学

Article

作者: Tavasoli, Mahtab ; McMaster, Christopher R ; Chipurupalli, Sandhya

A review.The major membrane phospholipid phosphatidylcholine is predominantly synthesized through the CDP-choline (Kennedy) pathway at the endoplasmic reticulum (ER).The first step in this pathway is the phosphorylation of choline by choline kinase.Humans contain two choline kinase isoforms, CHKA and CHKB.ER-phagy results in engulfment of sections of ER into autophagosomes and transport to lysosomes to aid in replenishment/recycling of damaged ER.The mCherry puncta were also observed when fed cells were treated with the choline kinase inhibitor EB3D.These data suggest that ER-phagy occurs upon inhibition of choline kinase and ER-phagy could play a role in the etiol. of diseases associated with choline kinase inhibition.

2022-06-30·Brain1区 · 医学

Bi-allelic variants inCHKAcause a neurodevelopmental disorder with epilepsy and microcephaly

1区 · 医学

Article

作者: Maroofian, Reza ; Fernández-Murray, J Pedro ; Williams, Jason ; Kaur, Parneet ; Darvish, Hossein ; Jamra, Rami Abou ; Scholle, Leila Motlagh ; Klöckner, Chiara ; Merkenschlager, Andreas ; Girisha, Katta Mohan ; Kruer, Michael C ; Noureldeen, Mahmoud M ; Cali, Elisa ; McMaster, Christopher R ; Banu, Selina ; Pagnozzi, Alex ; Bakhtiari, Somayeh ; Efthymiou, Stephanie ; Tavasoli, Mahtab ; Zaki, Maha S ; Platzer, Konrad ; Houlden, Henry ; Firouzabadi, Saghar Ghasemi ; Sticht, Heinrich ; Nahar, Kamrun ; Stoltenburg-Didinger, Gisela ; Narayanan, Dhanya Lakshmi ; Shukla, Anju ; Gburek-Augustat, Janina

AbstractThe Kennedy pathways catalyse the de novo synthesis of phosphatidylcholine and phosphatidylethanolamine, the most abundant components of eukaryotic cell membranes. In recent years, these pathways have moved into clinical focus because four of ten genes involved have been associated with a range of autosomal recessive rare diseases such as a neurodevelopmental disorder with muscular dystrophy (CHKB), bone abnormalities and cone-rod dystrophy (PCYT1A) and spastic paraplegia (PCYT2, SELENOI).We identified six individuals from five families with bi-allelic variants in CHKA presenting with severe global developmental delay, epilepsy, movement disorders and microcephaly. Using structural molecular modelling and functional testing of the variants in a cell-based Saccharomyces cerevisiae model, we determined that these variants reduce the enzymatic activity of CHKA and confer a significant impairment of the first enzymatic step of the Kennedy pathway.In summary, we present CHKA as a novel autosomal recessive gene for a neurodevelopmental disorder with epilepsy and microcephaly.

2019-08-15·Human Molecular Genetics

Functional rescue in a mouse model of congenital muscular dystrophy with megaconial myopathy

Article

作者: Sukoff Rizzo, Stacey J ; Sayed-Zahid, Ambreen A ; Sher, Roger B ; Cox, Gregory A ; Patenaude, Kathryn E ; Anderson, Laura C

AbstractCongenital muscular dystrophy with megaconial myopathy (MDCMC) is an autosomal recessive disorder characterized by progressive muscle weakness and wasting. The observation of megamitochondria in skeletal muscle biopsies is exclusive to this type of MD. The disease is caused by loss of function mutations in the choline kinase beta (CHKB) gene which results in dysfunction of the Kennedy pathway for the synthesis of phosphatidylcholine. We have previously reported a rostrocaudal MD (rmd) mouse with a deletion in the Chkb gene resulting in an MDCMC-like phenotype, and we used this mouse to test gene therapy strategies for the rescue and alleviation of the dystrophic phenotype. Introduction of a muscle-specific Chkb transgene completely rescues motor and behavioral function in the rmd mouse model, confirming the cell-autonomous nature of the disease. Intramuscular gene therapy post-disease onset using an adeno-associated viral 6 (AAV6) vector carrying a functional copy of Chkb is also capable of rescuing the dystrophy phenotype. In addition, we examined the ability of choline kinase alpha (Chka), a gene paralog of Chkb, to improve dystrophic phenotypes when upregulated in skeletal muscles of rmd mutant mice using a similar AAV6 vector. The sum of our results in a preclinical model of disease suggest that replacement of the Chkb gene or upregulation of endogenous Chka could serve as potential lines of therapy for MDCMC patients.