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Relationship between epigenetic factors and retrotransposons and the etiopathogenesis of neurodegenerative diseases

Year: 2025

Type: article

Abstract: The pathogenesis of neurodegenerative diseases is associated with proteopathy and the abnormal aggregation of specific proteins, including amyloid-β and tau protein in Alzheimer's disease, α-synuclein in Parikinson disease, and TDP-43 and FUS in amyotrophic lateral sclerosis. Etiological factors may include viral infections because of the protective functions of the above proteins in relation to specific viruses. In turn, the latter may enhance the expression of retroelements. Another cause of neurodegenerative diseases is physiological aging, as it activates retroelements and is associated with proteopathy of antiviral proteins, which normally suppresses the expression of retroelements. It is assumed that the etiological factors of amyotrophic lateral sclerosis, Alzheimer disease, and Parkinson disease include the associated genetic polymorphisms, most of which localize within intronic and intergenic regions where retroelement genes are located. Thus, the etiological factors of neurodegenerative diseases include genetic predisposition to the excessive activation of retroelements, aging, and viral infections, thus causing pathogenic proteopathy and the aggregation of amyloid-β, tau protein, α-synuclein, TDP-43, and FUS. As a result, these proteins lose their ability to inhibit retroelements by causing their excessive activation and an inflammatory immune response to their transcripts. In turn, the expression products of polymorphic retroelements enhance the production of antiviral proteins and their proteopathy and aggregation. A vicious circle develops that promotes the progression of the condition; this circle may be broken by inhibitors of retroelements and specific microRNAs that may become the basis for targeted therapy for neurodegenerative diseases. As such, these processes do not induce nucleotide DNA sequence damage; rather, they indicate the epigenetic mechanisms of these diseases.

Source: Kazan medical journal

DOI: 10.17816/kmj641725

Author: Rustam N. Mustafin

Institution: Bashkir State Medical University

Language: English

Topic: Alzheimer's disease research and treatments

Subfield: Physiology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $93