期刊
ASIAN JOURNAL OF PSYCHIATRY
卷 39, 期 -, 页码 174-177出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ajp.2018.08.010
关键词
Alzheimer's disease; B-lymphocytes; Cell cycle; Dysregulation; Genes; Retinoic acid
类别
资金
- Department of Biotechnology [BT/01/CEIB/11/VI/11]
- INSPIRE fellowship of the Department of Science and Technology, Government of India
- Accelerator program for discovery in brain disorders using stem cells (ADBS)
- Department of Biotechnology, Government of India
- Pratiksha trust
- Ramalingaswamy re-entry fellowship of the Department of Biotechnology, Government of India
Aberrant re-entry of neurons into cell cycle appears to be an early event in Alzheimer's disease (AD) and targeting this dysregulation may have therapeutic potential. We have examined whether cell cycle dysregulation in AD can be detected using patient and control derived B-lymphocytes. Cell cycle analysis using flow cytometry demonstrated that cell cycle dysregulation occurs in AD lymphocytes, with a significant difference in the distribution of cells in GO/G1, S and G2/M phases of cell cycle as compared to control lymphocytes. Using global gene expression analysis by RNA sequencing and cell cycle analysis, we examined the role of Retinoic Acid (RA), a candidate molecule predicted to be of therapeutic potential in cell cycle dysregulation associated with AD. CCND1, CCNE2, E2F transcription factors which are known to be dysregulated in AD were among the 32 genes that showed differential expression in response to RA treatment thus suggesting a protective role of RA. However, the cell cycle analysis demonstrated that RA did not reverse the cellular phenotype in AD lymphocytes. This suggests that though RA might have a protective role by influencing the expression of cell cycle genes, it might not be able to arrest abnormal re-entry into cell cycle.
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