中国神经再生研究(英文版) ›› 2021, Vol. 16 ›› Issue (7): 1438-1439.doi: 10.4103/1673-5374.301013

• 观点:神经损伤修复保护与再生 • 上一篇    下一篇

簇蛋白:大脑中的多面蛋白质

  

  • 出版日期:2021-07-15 发布日期:2021-01-07

Clusterin: a multifaceted protein in the brain

Hee-Jung Moon, Sarah K. Herring, Liqin Zhao*   

  1. Department of Pharmacology and Toxicology, School of Pharmacy, University of Kansas, Lawrence, KS, USA (Moon HJ, Herring SK, Zhao L)
    Neuroscience Graduate Program, University of Kansas, Lawrence, KS, USA (Zhao L)
    Current address: Citoxlab A Charles River Company, Stilwell, KS, USA (Herring SK)
  • Online:2021-07-15 Published:2021-01-07
  • Contact: Liqin Zhao, PhD,lzhao@ku.edu.
  • Supported by:
    The present work was supported by the National Institutes of Health (NIH; R21AG055964, R21AG059177, R01AG061038 to LZ). 

摘要: https://orcid.org/0000-0002-0491-6943 
(Liqin Zhao) 

Abstract: Late-onset Alzheimer’s disease (LOAD), the most common cause of dementia, currently affects 5.6 million Americans ages 65 and older. LOAD is a neurodegenerative disorder characterized by progressive loss in synaptic function, notable bioenergetic decline, increased neuronal death and brain atrophy, and significant cognitive impairment. Because the etiology of LOAD remains unknown, a treatment for LOAD has not yet been formulated, a fact that is clearly demonstrated by the more than 200 failed clinical trials. These failures underscore the significance of identifying the LOAD risk mechanisms that would allow early intervention in the preclinical stage of LOAD. Genome-wide association studies have identified more than a dozen genetic risk variants that are associated with the development of LOAD. Clusterin (CLU), also known as apolipoprotein J (APOJ), has been established as the third most prominent genetic risk factor for LOAD after apolipoprotein E (APOE) and bridging integrator 1 (BIN1) (Harold et al., 2009; Lambert et al., 2009). A number of single nucleotide polymorphisms (SNPs) within the CLU locus, with the majority being intronic, have been linked to significantly altered LOAD risk, independent of APOE status (Figure 1A; (Medical Genetics and Human Variation, 2019)); however, it is unclear how these SNPs affect CLU mRNA, protein isoform expression and function.