Nair Ayushi, Greeny Alosh, Rajendran Rajalakshmi, Abdelgawad Mohamed A, Ghoneim Mohammed M, Raghavan Roshni Pushpa, Sudevan Sachithra Thazhathuveedu, Mathew Bijo, Kim Hoon
Department of Pharmacy Practice, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, Amrita Health Science Campus, Kochi 682041, India.
Department of Pharmaceutical Chemistry, College of Pharmacy, Jouf University, Sakaka, Al Jouf 72341, Saudi Arabia.
Pharmaceuticals (Basel). 2023 Jan 19;16(2):147. doi: 10.3390/ph16020147.
KIF1A-associated neurological diseases (KANDs) are a group of inherited conditions caused by changes in the microtubule (MT) motor protein KIF1A as a result of gene mutations. Anterograde transport of membrane organelles is facilitated by the kinesin family protein encoded by the MT-based motor gene . Variations in the gene, which primarily affect the motor domain, disrupt its ability to transport synaptic vesicles containing synaptophysin and synaptotagmin leading to various neurological pathologies such as hereditary sensory neuropathy, autosomal dominant and recessive forms of spastic paraplegia, and different neurological conditions. These mutations are frequently misdiagnosed because they result from spontaneous, non-inherited genomic alterations. Whole-exome sequencing (WES), a cutting-edge method, assists neurologists in diagnosing the illness and in planning and choosing the best course of action. These conditions are simple to be identified in pediatric and have a life expectancy of 5-7 years. There is presently no permanent treatment for these illnesses, and researchers have not yet discovered a medicine to treat them. Scientists have more hope in gene therapy since it can be used to cure diseases brought on by mutations. In this review article, we discussed some of the experimental gene therapy methods, including gene replacement, gene knockdown, symptomatic gene therapy, and cell suicide gene therapy. It also covered its clinical symptoms, pathogenesis, current diagnostics, therapy, and research advances currently occurring in the field of KAND-related disorders. This review also explained the impact that gene therapy can be designed in this direction and afford the remarkable benefits to the patients and society.
KIF1A相关神经疾病（KANDs）是一组遗传性疾病，由基因突变导致微管（MT）运动蛋白KIF1A发生变化引起。基于MT的运动基因编码的驱动蛋白家族蛋白促进膜细胞器的顺向运输。该基因的变异主要影响运动结构域，破坏其运输含有突触素和突触结合蛋白的突触小泡的能力，导致各种神经病理学疾病，如遗传性感觉神经病、常染色体显性和隐性痉挛性截瘫以及其他不同的神经疾病。这些突变常被误诊，因为它们是由自发的、非遗传的基因组改变引起的。全外显子组测序（WES）作为一种前沿方法，有助于神经科医生诊断疾病并规划和选择最佳治疗方案。这些疾病在儿科容易识别，预期寿命为5至7年。目前这些疾病尚无根治方法，研究人员也尚未发现治疗它们的药物。科学家们对基因治疗寄予更多希望，因为它可用于治疗由突变引起的疾病。在这篇综述文章中，我们讨论了一些实验性基因治疗方法，包括基因替代、基因敲低、对症基因治疗和细胞自杀基因治疗。文章还涵盖了其临床症状、发病机制、当前诊断方法、治疗方法以及KAND相关疾病领域目前的研究进展。这篇综述还解释了可以朝这个方向设计基因治疗并为患者和社会带来显著益处的影响。
