{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T21:30:24Z","timestamp":1790890224113,"version":"4.1.0"},"reference-count":81,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2024,8,6]],"date-time":"2024-08-06T00:00:00Z","timestamp":1722902400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Alpha-synuclein (\u03b1Syn) aggregates are the primary component of Lewy bodies, which are pathological hallmarks of Parkinson\u2019s disease (PD). The toxicity of \u03b1Syn seems to increase with its elevated expression during injury, suggesting that therapeutic approaches focused on reducing \u03b1Syn burden in neurons could be beneficial. Additionally, studies have shown higher levels of SNCA mRNA in the midbrain tissues and substantia nigra dopaminergic neurons of sporadic PD post-mortem brains compared to controls. Therefore, the regulation of SNCA expression and inhibition of \u03b1Syn synthesis could play an important role in the pathogenesis of injury, resulting in an effective treatment approach for PD. In this context, we summarized the most recent and innovative strategies proposed that exploit the targeting of SNCA to regulate translation and efficiently knock down cytoplasmatic levels of \u03b1Syn. Significant progress has been made in developing antisense technologies for treating PD in recent years, with a focus on antisense oligonucleotides and short-interfering RNAs, which achieve high specificity towards the desired target. To provide a more exhaustive picture of this research field, we also reported less common but highly innovative strategies, including small molecules, designed to specifically bind 5\u2032-untranslated regions and, targeting secondary nucleic acid structures present in the SNCA gene, whose formation can be modulated, acting as a transcription and translation control. To fully describe the efficiency of the reported strategies, the effect of \u03b1Syn reduction on cellular viability and dopamine homeostasis was also considered.<\/jats:p>","DOI":"10.3390\/biom14080949","type":"journal-article","created":{"date-parts":[[2024,8,6]],"date-time":"2024-08-06T11:54:19Z","timestamp":1722945259000},"page":"949","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Novel Therapeutic Horizons: SNCA Targeting in Parkinson\u2019s Disease"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8887-4276","authenticated-orcid":false,"given":"Alessio Maria","family":"Caramiello","sequence":"first","affiliation":[{"name":"Department of Chemistry, University of Pavia, Viale Taramelli 10, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6683-1726","authenticated-orcid":false,"given":"Valentina","family":"Pirota","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Pavia, Viale Taramelli 10, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1111\/ene.14108","article-title":"Parkinson disease","volume":"27","author":"Balestrino","year":"2020","journal-title":"Eur. 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