ArticleNature communications2026
Development of an RNA aptamer as a therapeutic agent for synucleinopathies.
Article in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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13 authors.
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Abstract
The aggregation of α-synuclein (αSyn), a 140-mer protein, has been implicated in the pathogenesis of Parkinson's disease, multiple system atrophy, and dementia with Lewy bodies. KTKEGV pseudo-repeats (KRs) in the sequence of αSyn are key mediators of its prion-like propagation and neurodegeneration. Despite the availability of symptomatic treatments, no current therapy effectively delays disease progression. Here we report a 77-nucleotide RNA aptamer called 1R6, obtained through in vitro selection, that binds with high affinity and selectivity to αSyn1-95. 1R6 significantly inhibits αSyn oligomerization and β-sheet-rich fibril assembly and promotes disaggregation of preformed fibrils. Additionally, 1R6 suppresses αSyn seeding, as determined by a FRET-based biosensor-cell assay. Cellular studies reveal that 1R6 co-transfection completely prevents αSyn-induced cytotoxicity. To assess the protective effects of 1R6 in vivo, we use a Drosophila melanogaster model expressing human αSyn in neurons. Flies fed 1R6 show improved locomotor activity, reduced photoreceptor degeneration, and decreased αSyn levels in the head. Structural characterization using
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