Transposable elements as new players in neurodegenerative diseases. Issue 22 (18th October 2021)

• Record Type: Journal Article
• Authors: Ravel‐Godreuil, Camille; Znaidi, Rania; Bonnifet, Tom; Joshi, Rajiv L.; Fuchs, Julia
• Is Part Of: FEBS letters. Volume 595:Issue 22(2021)
• Page Start: 2733
• Page End: 2755
• Publication Date: 2021-10-18
• Subjects: aging -- Alzheimer's disease -- gene dysregulation -- genomic instability -- heterochromatin destructuration -- neurodegenerative diseases -- neuroinflammation -- oxidative stress -- Parkinson disease -- retrotransposons; Biochemistry -- Periodicals; Biophysics -- Periodicals; Molecular biology -- Periodicals; Biochimie -- Périodiques; Biochemistry; Biophysics; Molecular biology; Periodicals; 572.05
• DOI: 10.1002/1873-3468.14205
• Languages: English
• ISSNs: 0014-5793

Abstract

Abstract : 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. Abstract : Transposable elements (TEs) are emerging as new culprits in the pathogenic pathways leading to neurodegeneration in aging‐related neurodegenerative diseases.