From the RNA World to the Clinic: RNA Therapeutics for Substance Use Disorders

Öz

RNA therapeutics are a rapidly expanding category of drugs that aim to treat or prevent diseases. Since the mechanism of substance addiction is not fully elucidated, there are still great difficulties in its prevention and treatment. It is known that long-term intake of addictive substances modulates the gene expression profile and causes pathological neuroadaptation in brain regions related to reward mechanisms and memory. Although non-coding RNAs have been shown to regulate maladaptive neuroadaptations that drive compulsive substance use, their effect on substance use disorder has not yet been clinically tested. This study aims to focus on non-coding RNA-based therapeutics as a potential approach to the treatment of substance use disorder. In this perspective, non-coding RNA processes involved in substance use disorder are reviewed. Recent therapeutic approaches for targeting non-coding RNAs are discussed, highlighting the potential opportunities and challenges of noncoding RNA-targeting therapeutics for substance use disorder. In conclusion, the mechanisms of action of RNA modulation in the treatment of various diseases have become a promising strategy, leading to the conclusion that noncoding RNAs should be explored as applicable therapeutic targets in the treatment of substance use disorder.

Anahtar Kelimeler

• Substance use disorder
• RNA
• Noncoding RNA
• RNA therapeutics

RNA Dünyasından Kliniğe: Madde Kullanım Bozuklukları için RNA Terapötikleri

Öz

RNA terapötikleri, hastalıkları tedavi etmeyi veya önlemeyi amaçlayan ve hızla genişleyen bir ilaç kategorisidir. Madde bağımlılığının mekanizması tam olarak aydınlatılamadığından, önlenmesi ve tedavisinde halen büyük zorluklar yaşanmaktadır. Bağımlılık yapan maddelerin uzun süreli alımının gen ekspresyon profilini modüle ettiği, ödül mekanizması ve hafıza ile ilgili beyin bölgelerinde patolojik nöroadaptasyona yol açtığı bilinmektedir. Kodlamayan RNA’ların, kompulsif madde kullanımını yönlendiren uyumsuz nöroadaptasyonları düzenlediği gösterilmiş olsa da madde kullanım bozukluğu üzerindeki etkisi henüz klinik olarak test edilmemiştir. Bu gözden geçirme çalışması, madde kullanım bozukluğunun tedavisine yönelik potansiyel bir yaklaşım olan, kodlamayan RNA bazlı terapötiklere odaklanmayı amaçlamaktadır. Bu perspektifte, madde kullanım bozukluğunda yer alan kodlamayan RNA süreçleri gözden geçirilmiştir. Kodlamayan RNA'ları hedeflemeye yönelik son terapötik yaklaşımlar tartışılarak, madde kullanım bozukluğu için kodlamayan RNA'yı hedefleyen terapötiklerin potansiyel fırsatları ve zorlukları vurgulanmıştır. Sonuç olarak, RNA modülasyonunun çeşitli hastalıkların tedavisindeki etki mekanizmalarının umut verici bir strateji haline gelmesi, kodlamayan RNA'ların madde kullanım bozukluğunun tedavisinde de uygulanabilir terapötik hedefler olarak keşfedilmesi gerektiği kanaati oluşturmaktadır.

Anahtar Kelimeler

• Madde kullanım bozukluğu
• RNA
• Kodlamayan RNA
• RNA terapötikleri

Kaynakça

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