Department of Pharmacology, University of Minnesota, Minneapolis, MN 55455, USA.
Nutrients. 2022 Apr 6;14(7):1528. doi: 10.3390/nu14071528.
In this review, we discuss the emerging role of Cellular Retinoic Acid Binding Protein 1 (CRABP1) as a mediator of non-canonical activities of retinoic acid (RA) and relevance to human diseases. We first discuss the role of CRABP1 in regulating MAPK activities and its implication in stem cell proliferation, cancers, adipocyte health, and neuro-immune regulation. We then discuss an additional role of CRABP1 in regulating CaMKII activities, and its implication in heart and motor neuron diseases. Through molecular and genetic studies of knockout (CKO) mouse and culture models, it is established that CRABP1 forms complexes with specific signaling molecules to function as RA-regulated signalsomes in a cell context-dependent manner. Gene expression data and gene single nucleotide polymorphisms (SNPs) of human cancer, neurodegeneration, and immune disease patients implicate the potential association of abnormality in CRABP1 with human diseases. Finally, therapeutic strategies for managing certain human diseases by targeting CRABP1 are discussed.
在这篇综述中,我们讨论了细胞视黄酸结合蛋白 1(CRABP1)作为视黄酸(RA)非经典活性的介质的新作用及其与人类疾病的相关性。我们首先讨论了 CRABP1 在调节 MAPK 活性及其在干细胞增殖、癌症、脂肪细胞健康和神经免疫调节中的作用。然后,我们讨论了 CRABP1 在调节 CaMKII 活性中的另一个作用,及其在心脏和运动神经元疾病中的作用。通过对基因敲除(CKO)小鼠和培养模型的分子和遗传研究,确立了 CRABP1 与特定信号分子形成复合物,以细胞上下文依赖的方式作为 RA 调节的信号转导物发挥作用。人类癌症、神经退行性疾病和免疫性疾病患者的基因表达数据和基因单核苷酸多态性(SNPs)表明,CRABP1 的异常与人类疾病可能存在关联。最后,讨论了通过靶向 CRABP1 来治疗某些人类疾病的治疗策略。