The Role of Retrotransposons and Endogenous Retroviruses in Age-Dependent Neurodegenerative Disorders.
Annu Rev Neurosci
; 47(1): 123-143, 2024 Aug.
Article
em En
| MEDLINE
| ID: mdl-38663088
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.
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Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Envelhecimento
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Retroelementos
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Doenças Neurodegenerativas
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Retrovirus Endógenos
Limite:
Animals
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Humans
Idioma:
En
Revista:
Annu Rev Neurosci
Ano de publicação:
2024
Tipo de documento:
Article