Hapln2 in Neurological Diseases and Its Potential as Therapeutic Target.

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

doi:10.3389/fnagi.2019.00060

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.

Highlights

Parkinson’s disease (PD), Alzheimer’s disease (AD) and schizophrenia are neurological diseases characterized by the dysfunction of certain types of neurons (Hardy and Higgins, 1992; Korth, 2012; Ghosh et al, 2016)
Substrates for degradation within this pathway are specified by E3 ubiquitin ligases (Ardley and Robinson, 2005), and we recently demonstrated that the E3 ubiquitin ligases Hrd1, Gp78 and Parkin colocalized with hyaluronan and proteoglycan link protein 2 (Hapln2; Wang et al, 2016)
Studies have shown that Hapln2, known as brain-derived link protein1 (Bral1), is vital for neuronal conductivity and the formation of the extracellular matrix (ECM), and besides its potential role in the ubiquitin-proteasome pathway (UPP), it has been identified as a contributor to the pathological processes in several neurological disorders

Summary

Introduction

Parkinson’s disease (PD), Alzheimer’s disease (AD) and schizophrenia are neurological diseases characterized by the dysfunction of certain types of neurons (Hardy and Higgins, 1992; Korth, 2012; Ghosh et al, 2016). Studies have shown that Hapln2, known as brain-derived link protein1 (Bral1), is vital for neuronal conductivity and the formation of the extracellular matrix (ECM), and besides its potential role in the UPP, it has been identified as a contributor to the pathological processes in several neurological disorders. Martins-de-Souza et al (2009) showed that the expression levels of Hapln2 in the anterior temporal lobe are lower in patients with schizophrenia than those of the control subjects, and Minjarez et al (2013) suggested that Hapln2 was probably in the neurofibrillary tangles (NFTs) from AD brain.

Results

Conclusion