The Role of Retrotransposons and Endogenous Retroviruses in Age-Dependent Neurodegenerative Disorders
Year: 2024
Type: review
Abstract: Over 40% of the human genome is composed of retrotransposons, DNA species that hold the potential to replicate via an RNA intermediate and are evolutionarily related to retroviruses. Retrotransposons are most studied for their ability to jump within a genome, which can cause DNA damage and novel insertional mutations. Retrotransposon-encoded products, including viral-like proteins, double-stranded RNAs, and extrachromosomal circular DNAs, can also be potent activators of the innate immune system. A growing body of evidence suggests that retrotransposons are activated in age-related neurodegenerative disorders and that such activation causally contributes to neurotoxicity. Here we provide an overview of retrotransposon biology and outline evidence of retrotransposon activation in age-related neurodegenerative disorders, with an emphasis on those involving TAR-DNA binding protein-43 (TDP-43) and tau. Studies to date provide the basis for ongoing clinical trials and hold promise for innovative strategies to ameliorate the adverse effects of retrotransposon dysregulation in neurodegenerative disorders.
Source: Annual Review of Neuroscience
Authors: Bess Frost, Josh Dubnau
Language: English
Subfield: Plant Science
Domain: Life Sciences
Open Access status: hybrid
Awards: Investigating the role of transposable element dysregulation as a driver of neurotoxicity in tauopathy, Brain aging and Alzheimer's related dementias: convergence onto retrotransposons and endogenous retroviruses, Feedback amplification between Retrotransposons/endogenous retroviruses and TDP-43 in Alzheimers related dementias
OpenAlex ID: W4395448296