Porel Pratyush, Hunjan Garry, Kaur Navpreet, Sharma Vipul, Kaur Manpreet, Mittal Yukti, Kaur Ramandeep, Aran Khadga Raj
Department of Pharmacology, ISF College of Pharmacy, Moga, Punjab, 142001, India.
Department of Pharmacy Practice, ISF College of Pharmacy, Moga, Punjab, 142001, India.
Metab Brain Dis. 2025 May 29;40(5):213. doi: 10.1007/s11011-025-01629-3.
Peptide nucleic acids (PNAs) are synthetic nucleic acid analogues offering distinct structural and functional advantages over conventional RNA and DNA, positioning them as powerful molecules in molecular biology. Recently, PNAs have gained significant attention for their potential in the prevention and management of neurological diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), stroke, traumatic brain injury (TBI), spinal cord injury (SCI), depression, and anxiety. PNA5, a specific PNA variant, is highly expressed in neocortical association regions, particularly in primates, and plays a critical role in high-level cognitive functions such as reasoning, decision-making, and problem-solving. It can form stable, sequence-specific hybridizations with nucleic acids, resist nuclease degradation, and efficiently cross cellular membranes, making them ideal candidates for targeting disease-related genes in the brain. PNA5 has shown neuroprotective properties by improving cognitive function, reducing neuroinflammation, and preserving the integrity of the blood-brain barrier (BBB). Additionally, it supports critical processes such as neural migration, axon guidance, and synaptogenesis, which are vital for maintaining proper brain function. This review explores the mechanisms by which PNAs, particularly PNA5, exert therapeutic effects in neurological disorders. It highlights their role in gene modulation, protein regulation, and potential strategies for enhancing PNA delivery to the central nervous system (CNS) and its related disorders.
肽核酸（PNA）是一种合成核酸类似物，与传统的RNA和DNA相比具有独特的结构和功能优势，使其成为分子生物学中强大的分子。最近，PNA因其在预防和管理神经疾病方面的潜力而受到广泛关注，这些疾病包括阿尔茨海默病（AD）、帕金森病（PD）、多发性硬化症（MS）、亨廷顿舞蹈症（HD）、肌萎缩侧索硬化症（ALS）、中风、创伤性脑损伤（TBI）、脊髓损伤（SCI）、抑郁症和焦虑症。PNA5是一种特定的PNA变体，在新皮质联合区域高度表达，尤其是在灵长类动物中，并且在诸如推理、决策和解决问题等高阶认知功能中发挥关键作用。它可以与核酸形成稳定的、序列特异性杂交体，抵抗核酸酶降解，并有效地穿过细胞膜，使其成为靶向大脑中疾病相关基因的理想候选物。PNA5已通过改善认知功能、减轻神经炎症和维持血脑屏障（BBB）的完整性显示出神经保护特性。此外，它支持神经迁移、轴突导向和突触形成等关键过程，这些过程对于维持大脑正常功能至关重要。本综述探讨了PNA，特别是PNA5在神经疾病中发挥治疗作用的机制。它强调了它们在基因调节、蛋白质调控中的作用，以及增强PNA向中枢神经系统（CNS）及其相关疾病递送的潜在策略。
