Regulator of Cell Cycle (RGCC) Expression during the Progression of Alzheimer's Disease

Author:

Counts Scott E.123,Mufson Elliott J.45

Affiliation:

1. Department of Translational Science and Molecular Medicine, Michigan State University, Grand Rapids, MI, USA

2. Department of Family Medicine, Michigan State University, Grand Rapids, MI, USA

3. Hauenstein Neurosciences Center, Mercy Health Saint Mary's Hospital, Grand Rapids, MI, USA

4. Department of Neurobiology, Barrow Neurological Institute, Phoenix, AZ, USA

5. Department of Neurology, Barrow Neurological Institute, Phoenix, AZ, USA

Abstract

Unscheduled cell cycle reentry of postmitotic neurons has been described in cases of mild cognitive impairment (MCI) and Alzheimer's disease (AD) and may form a basis for selective neuronal vulnerability during disease progression. In this regard, the multifunctional protein regulator of cell cycle (RGCC) has been implicated in driving G1/S and G2/M phase transitions through its interactions with cdc/cyclin-dependent kinase 1 (cdk1) and is induced by p53, which mediates apoptosis in neurons. We tested whether RGCC levels were dysregulated in frontal cortex samples obtained postmortem from subjects who died with a clinical diagnosis of no cognitive impairment (NCI), MCI, or AD. RGCC mRNA and protein levels were upregulated by ~50%-60% in MCI and AD compared to NCI, and RGCC protein levels were associated with poorer antemortem global cognitive performance in the subjects examined. To test whether RGCC might regulate neuronal cell cycle reentry and apoptosis, we differentiated neuronotypic PC12 cultures with nerve growth factor (NGF) followed by NGF withdrawal to induce abortive cell cycle activation and cell death. Experimental reduction of RGCC levels increased cell survival and reduced levels of the cdk1 target cyclin B1. RGCC may be a candidate cell cycle target for neuroprotection during the onset of AD.

Publisher

SAGE Publications

Subject

Transplantation,Cell Biology,Biomedical Engineering

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3