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Hapln2在神经疾病中的作用及其作为治疗靶点的潜力。

Hapln2 in Neurological Diseases and Its Potential as Therapeutic Target.

作者信息

Wang Qinqin, Wang Chunmei, Ji Bingyuan, Zhou Jiawei, Yang Chunqing, Chen Jing

机构信息

Neurobiology Key Laboratory, Jining Medical University, Jining, China.

State Key Laboratory of Neuroscience, Institute of Neuroscience, Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, China.

出版信息

Front Aging Neurosci. 2019 Mar 21;11:60. doi: 10.3389/fnagi.2019.00060. eCollection 2019.

Abstract

Hyaluronan and proteoglycan link protein 2 (Hapln2) is important for the binding of chondroitin sulfate proteoglycans to hyaluronan. Hapln2 deficiency leads to the abnormal expression of extracellular matrix (ECM) proteins and dysfunctional neuronal conductivity, demonstrating the vital role of Hapln2 in these processes. Studies have revealed that Hapln2 promotes the aggregation of α-synuclein, thereby contributing to neurodegeneration in Parkinson's disease (PD), and it was recently suggested to be in intracellular neurofibrillary tangles (NFTs). Additionally, the expression levels of Hapln2 showed lower in the anterior temporal lobes of individuals with schizophrenia than those of healthy subjects. Together, these studies implicate the involvement of Hapln2 in the pathological processes of neurological diseases. A better understanding of the function of Hapln2 in the central nervous system (CNS) will provide new insights into the molecular mechanisms of these diseases and help to establish promising therapeutic strategies. Herein, we review the recent progress in defining the role of Hapln2 in brain physiology and pathology.

摘要

透明质酸和蛋白聚糖连接蛋白2(Hapln2)对于硫酸软骨素蛋白聚糖与透明质酸的结合很重要。Hapln2缺乏会导致细胞外基质(ECM)蛋白的异常表达和神经元传导功能障碍,表明Hapln2在这些过程中起着至关重要的作用。研究表明,Hapln2促进α-突触核蛋白的聚集,从而导致帕金森病(PD)中的神经退行性变,并且最近有人提出它存在于细胞内神经原纤维缠结(NFTs)中。此外,精神分裂症患者颞叶前部的Hapln2表达水平低于健康受试者。总之,这些研究表明Hapln2参与了神经疾病的病理过程。更好地了解Hapln2在中枢神经系统(CNS)中的功能将为这些疾病的分子机制提供新的见解,并有助于建立有前景的治疗策略。在此,我们综述了确定Hapln2在脑生理学和病理学中作用的最新进展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ee1/6437066/30e504fc6496/fnagi-11-00060-g0001.jpg

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