The role of Alu-derived RNAs in Alzheimer’s and other neurodegenerative conditions
| Autor: | Ancha Baranova, Max Myakishev-Rempel, Olga Nazarenko, Evgeniya Kananykhina, Astrid M. Roy-Engel, Yegor Vassetsky, Oksana Polesskaya, Irina Kulemzina |
|---|---|
| Přispěvatelé: | Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich) |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
RNA Untranslated Transcription Genetic Inflammasomes [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology Models Neurological Alu element Tretinoin Retinal Pigment Epithelium Biology 03 medical and health sciences Alu Elements Alzheimer Disease Transcription (biology) medicine Humans Neuroinflammation ComputingMilieux_MISCELLANEOUS Neurodegeneration Brain RNA Polymerase III RNA Neurodegenerative Diseases General Medicine medicine.disease Non-coding RNA Cell biology 030104 developmental biology biology.protein Human genome Dicer |
| Zdroj: | Medical Hypotheses Medical Hypotheses, Elsevier, 2018, 115, pp.29-34. ⟨10.1016/j.mehy.2018.03.008⟩ |
| ISSN: | 0306-9877 |
| Popis: | Non-coding RNAs have emerged as essential contributors to neuroinflammation. The Alu element is the most abundant potential source of non-coding RNA in the human genome represented by over 1.1 million copies totaling ∼10% of the genome's mass. Accumulation of "Alu RNA" was observed in the brains of individuals with dementia and Creutzfeldt-Jakob disease - a degenerative brain disorder. "Alu RNAs" activate inflammatory pathways and apoptosis in the non-neural cells. In particular, the "Alu RNA" cytotoxicity is suggested as a mechanism in retinal pigment epithelium (RPE), a compartment damaged in the process of age-related macular degeneration. In RPE cells, the deficiency of Dicer is reported to lead to an accumulation of P3Alu transcripts, subsequent activation of the ERK1/2 signaling pathway, and the formation of NLRP3 inflammasome. In turn, these events result in RPE cell death by apoptosis. Importantly, RPE cells are of neuroectodermal origin, these cells display more similarity to neurons than to other epithelial cells. Thus, it is plausible that the mechanisms of "Alu RNA" cytotoxicity in brain neurons are similar to that in RPE. We hypothesize that accumulation of polymerase III-transcribed noncoding RNA of Alu (P3Alu) may contribute to both neuroinflammation and neurodegeneration associated with Alzheimer's disease (AD) and other degenerative brain disorders. This hypothesis points toward a novel molecular pathway not previously considered for the treatment of AD. |
| Databáze: | OpenAIRE |
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