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Transposable elements as new players in neurodegenerative diseases
Author(s) -
RavelGodreuil Camille,
Znaidi Rania,
Bonnifet Tom,
Joshi Rajiv L.,
Fuchs Julia
Publication year - 2021
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.14205
Subject(s) - neurodegeneration , biology , neuroscience , neuroprotection , neuroinflammation , transposable element , genetics , disease , gene , medicine , genome , immunology , pathology , inflammation
Neurodegenerative diseases (NDs), including the most prevalent Alzheimer’s disease and Parkinson disease, share common pathological features. Despite decades of gene‐centric approaches, the molecular mechanisms underlying these diseases remain widely elusive. In recent years, transposable elements (TEs), long considered ‘junk’ DNA, have gained growing interest as pathogenic players in NDs. Age is the major risk factor for most NDs, and several repressive mechanisms of TEs, such as heterochromatinization, fail with age. Indeed, heterochromatin relaxation leading to TE derepression has been reported in various models of neurodegeneration and NDs. There is also evidence that certain pathogenic proteins involved in NDs ( e.g ., tau, TDP‐43) may control the expression of TEs. The deleterious consequences of TE activation are not well known but they could include DNA damage and genomic instability, altered host gene expression, and/or neuroinflammation, which are common hallmarks of neurodegeneration and aging. TEs might thus represent an overlooked pathogenic culprit for both brain aging and neurodegeneration. Certain pathological effects of TEs might be prevented by inhibiting their activity, pointing to TEs as novel targets for neuroprotection.