Hashmi Muhammad Abu Talha Safdar, Fatima Hooriya, Ahmad Sadia, Rehman Amna, Safdar Fiza
Department of Zoology University of Central Punjab Lahore Pakistan.
Institute of Zoology University of Punjab Lahore Pakistan.
Ibrain. 2024 Nov 11;10(4):395-426. doi: 10.1002/ibra.12183. eCollection 2024 Winter.
Neurodegenerative disorders encompass a group of age-related conditions characterized by the gradual decline in both the structure and functionality of the central nervous system (CNS). RNA modifications, arising from the epitranscriptome or RNA-modifying protein mutations, have recently been observed to contribute significantly to neurodegenerative disorders. Specific modifications like N6-methyladenine (m6A), N1-methyladenine (m1A), 5-methylcytosine (m5C), pseudouridine and adenosine-to-inosine (A-to-I) play key roles, with their regulators serving as crucial therapeutic targets. These epitranscriptomic changes intricately control gene expression, influencing cellular functions and contributing to disease pathology. Dysregulation of RNA metabolism, affecting mRNA processing and noncoding RNA biogenesis, is a central factor in these diseases. This review underscores the complex relationship between RNA modifications and neurodegenerative disorders, emphasizing the influence of RNA modification and the epitranscriptome, exploring the function of RNA modification enzymes in neurodegenerative processes, investigating the functional consequences of RNA modifications within neurodegenerative pathways, and evaluating the potential therapeutic advancements derived from assessing the epitranscriptome.
神经退行性疾病包括一组与年龄相关的病症,其特征是中枢神经系统(CNS)的结构和功能逐渐衰退。最近发现,由表观转录组或RNA修饰蛋白突变引起的RNA修饰在神经退行性疾病中起重要作用。特定修饰,如N6-甲基腺嘌呤(m6A)、N1-甲基腺嘌呤(m1A)、5-甲基胞嘧啶(m5C)、假尿苷和腺苷到肌苷(A到I)发挥关键作用,其调节剂作为关键治疗靶点。这些表观转录组变化复杂地控制基因表达,影响细胞功能并导致疾病病理。RNA代谢失调,影响mRNA加工和非编码RNA生物合成,是这些疾病的核心因素。本综述强调了RNA修饰与神经退行性疾病之间的复杂关系,强调了RNA修饰和表观转录组的影响,探讨了RNA修饰酶在神经退行性过程中的功能,研究了神经退行性途径中RNA修饰的功能后果,并评估了通过评估表观转录组获得的潜在治疗进展。