The final, formatted version of the article will be published soon.
PERSPECTIVE article
Front. Neurosci.
Sec. Neurodegeneration
Volume 18 - 2024 |
doi: 10.3389/fnins.2024.1445540
This article is part of the Research Topic Neuroinflammation and Neurodegenerative Diseases View all 9 articles
Neurodegenerative Diseases Reflect the Reciprocal Roles played by Retroelements in Regulating Memory and Immunity
Provisionally accepted- 1 Other, Charlestown, United States
- 2 InsideOutBio, Inc, Charlestown, Massachusetts, United States
Tetrapod endogenous retroelements (ERE) encode proteins that have been exapted to perform many roles in development and also in innate immunity, including GAG (group specific antigen) proteins from the ERE long terminal repeat (LTR) family, some of which can assemble into viral-like capsids (VLCs) and transmit mRNA across synapses. The best characterized member of this family is ARC (activity-regulated cytoskeletal gene), that is involved in memory formation. Other types of EREs, such as LINES and SINES (long and short interspersed elements), have instead been exapted for immune defenses against infectious agents. These immune EREs identify host transcripts by forming the unusual left-handed Z-DNA and Z-RNA conformations to enable self/nonself discrimination. Elevated levels of immune EREs in the brain are associated with neurodegenerative disease. Here I address the question of how pathways based on immune EREs are relate to the memory EREs that mediate neural plasticity. I propose that during infection and in other inflammatory states, ERE encoded GAG capsids deliver interferon-induced immune EREs that rapidly inhibit translation of viral RNAs in the dendritic splines by activation of protein kinase R (PKR). The response limits transmission of viruses and autonomously replicating elements, while protecting bystander cells from stress-induced cell death. Further, the PKR-dependent phosphorylation of proteins, like tau, disrupts the endocytic pathways exploited by viruses to spread to other cells. The responses come at a cost. They impair memory formation and can contribute to pathology by increasing the deposition of amyloid beta.
Keywords: flipons, Memory, Immunity & Antiviral strategies, PKR activation, ADAR1 deaminase, Retroelement's, Virus Like Capsids, Arc
Received: 07 Jun 2024; Accepted: 03 Sep 2024.
Copyright: © 2024 Herbert. 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) or licensor 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:
Alan Herbert, Other, Charlestown, United States
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.