Emerging Roles of miR-146a-5p in Multiple Sclerosis: Evidence from Recent Studies

Abstract

Multiple sclerosis is a complex neuroimmune disorder characterized by chronic inflammation, demyelination, and neurodegeneration. Among the various molecular players, microRNA-146a-5p has emerged as a critical, albeit complex, regulator of the neuroimmune landscape in MS. This review synthesizes recent evidence highlighting the dual role of miR-146a-5p, which primarily functions as an anti-inflammatory agent but can also contribute to pathology in a cell-type and context-dependent manner. Its expression is dynamically regulated in the central nervous system , cerebrospinal fluid, and blood, correlating with disease activity, treatment response, and clinical metrics such as the Expanded Disability Status Scale. We explore its compartmentalized dysregulation, notably in active gadolinium-enhancing lesions, and its potential as a sensitive diagnostic and prognostic biomarker. The involvement of miR-146a-5p in key cellular processes—including microglial activation, oligodendrocyte maturation, and astrocyte pathology—underscores its therapeutic relevance. Furthermore, we discuss its interaction with environmental factors like Vitamin D and its role in exosome-mediated intercellular communication. Preclinical studies demonstrating that manipulating miR-146a-5p levels can ameliorate neuroinflammation and promote remyelination solidify its promise as a novel therapeutic target. Future research should focus on elucidating its precise mechanisms across different cellular contexts and developing targeted delivery systems to translate these findings into effective miR-146a-5p-based interventions for MS.

Keywords

• Multiple Sclerosis
• miR-146a-5p
• biomarker
• microRNA
• neuroinflammation

Multiple Sklerozda miR-146a-5p’nin Ortaya Çıkan Rolleri: Güncel Çalışmalardan Kanıtlar

Abstract

Multipl skleroz, kronik inflamasyon, demiyelinizasyon ve nörodejenerasyon ile karakterize karmaşık bir nöroimmün hastalıktır. Çeşitli moleküler düzenleyiciler arasında, mikroRNA-146a-5p, MS’te nöroimmün ortamın kritik ancak karmaşık bir düzenleyicisi olarak öne çıkmıştır. Bu derleme, esas olarak anti-inflamatuvar bir düzenleyici olarak işlev görmesine rağmen, hücre tipine ve bağlama bağlı olarak patolojik süreçlere de katkıda bulunabilen miR-146a-5p’nin çift yönlü rolünü vurgulayan güncel kanıtları bir araya getirmektedir. miR-146a-5p’nin ekspresyonu merkezi sinir sistemi, beyin omurilik sıvısı ve kanda dinamik olarak düzenlenmekte; hastalık aktivitesi, tedavi yanıtı ve Genişletilmiş Özürlülük Durum Ölçeği (EDSS) gibi klinik göstergelerle ilişki göstermektedir. Aktif gadolinyumla zenginleşmiş lezyonlarda belirgin olan bölgesel düzensizliği ve duyarlı bir tanısal ve prognostik biyobelirteç olarak potansiyeli ele alınmıştır. miR-146a-5p’nin mikroglia aktivasyonu, oligodendrosit olgunlaşması ve astrosit patolojisi gibi temel hücresel süreçlerdeki rolü, terapötik önemini vurgulamaktadır. Ayrıca, D vitamini gibi çevresel faktörlerle etkileşimi ve eksozom aracılı hücreler arası iletişimdeki rolü de tartışılmıştır. miR-146a-5p düzeylerinin düzenlenmesinin nöroinflamasyonu hafiflettiğini ve remiyelinizasyonu desteklediğini gösteren preklinik çalışmalar, bu molekülün yeni bir terapötik hedef olarak potansiyelini pekiştirmektedir. Gelecekteki araştırmaların, farklı hücresel bağlamlarda miR-146a-5p’nin kesin etki mekanizmalarını aydınlatmaya ve bu bulguları MS için etkili miR-146a-5p temelli tedavilere dönüştürebilecek hedefe yönelik taşıma sistemleri geliştirmeye odaklanması gerekmektedir.

Keywords

• Multipl Skleroz
• miR-146a-5p
• biyobelirteç
• mikroRNA
• nöroinflamasyon

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