Into the fourth dimension: dysregulation of genome architecture in aging and Alzheimer’s disease
- 1Max-Delbrück-Centrum für Molekulare Medizin, Germany
- 2Physiology and Pharmacology, University of Western Ontario, Canada
Alzheimer’s disease (AD) is a progressive neurodegenerative disease characterized by synapse dysfunction and cognitive impairment. Understanding the development and progression of AD is challenging, as the disease is highly complex and multifactorial. Both environmental and genetic factors play a role in AD pathogenesis, highlighted by observations of complex DNA modifications at the single gene level, and by new evidence that also implicates changes in genome architecture in AD patients. The four-dimensional structure of chromatin in space and time is essential for context-dependent regulation of gene expression in post-mitotic neurons. Dysregulation of epigenetic processes have been observed in the aging brain and in patients with AD, though there is not yet agreement on the impact of these changes on transcription. New evidence shows that proteins involved in genome organization have altered expression and localization in the AD brain, suggesting that the genomic landscape may play a critical role in the development of AD. This review discusses the role of the chromatin organizers and epigenetic modifiers in post-mitotic cells, the aging brain, and in the development and progression of AD. How these new insights can be used to help determine disease risk and inform treatment strategies will also be discussed.
Keywords: Alzheimer’s disease, epigenetics, gene regulation, Genome architecture, Protein mislocalization
Received: 29 Oct 2017;
Accepted: 13 Feb 2018.
Edited by:Detlev Boison, Legacy Health, United States
Reviewed by:Luc Buee, Institut National de la Santé et de la Recherche Médicale (INSERM), France
Claes Wahlestedt, Leonard M. Miller School of Medicine, United States
Copyright: © 2018 Winick-Ng and Rylett. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Dr. Warren Winick-Ng, Max-Delbrück-Centrum für Molekulare Medizin, Berlin, Germany, firstname.lastname@example.org