Neuroscience Research Center, Faculty of Medical Sciences, Lebanese University, Beirut, Lebanon.
J Neurosci Res. 2024 Apr;102(4):e25321. doi: 10.1002/jnr.25321.
Neurodegenerative diseases are progressive disorders characterized by synaptic loss and neuronal death. Optogenetics combines optical and genetic methods to control the activity of specific cell types. The efficacy of this approach in neurodegenerative diseases has been investigated in many reviews, however, none of them tackled it systematically. Our study aimed to review systematically the findings of optogenetics and its potential applications in animal models of chronic neurodegenerative diseases and compare it with deep brain stimulation and designer receptors exclusively activated by designer drugs techniques. The search strategy was performed based on the PRISMA guidelines and the risk of bias was assessed following the Systematic Review Centre for Laboratory Animal Experimentation tool. A total of 247 articles were found, of which 53 were suitable for the qualitative analysis. Our data revealed that optogenetic manipulation of distinct neurons in the brain is efficient in rescuing memory impairment, alleviating neuroinflammation, and reducing plaque pathology in Alzheimer's disease. Similarly, this technique shows an advanced understanding of the contribution of various neurons involved in the basal ganglia pathways with Parkinson's disease motor symptoms and pathology. However, the optogenetic application using animal models of Huntington's disease, multiple sclerosis, and amyotrophic lateral sclerosis was limited. Optogenetics is a promising technique that enhanced our knowledge in the research of neurodegenerative diseases and addressed potential therapeutic solutions for managing these diseases' symptoms and delaying their progression. Nevertheless, advanced investigations should be considered to improve optogenetic tools' efficacy and safety to pave the way for their translatability to the clinic.
神经退行性疾病是一种进行性疾病，其特征是突触丧失和神经元死亡。光遗传学结合了光学和遗传学方法来控制特定细胞类型的活性。许多综述都研究了这种方法在神经退行性疾病中的疗效，但没有一个系统地研究过它。我们的研究旨在系统地回顾光遗传学及其在慢性神经退行性疾病动物模型中的潜在应用，并将其与深部脑刺激和专门设计的受体药物技术进行比较。搜索策略是根据 PRISMA 指南进行的，风险偏倚是按照系统评价中心的实验室动物实验工具进行评估的。共发现 247 篇文章，其中 53 篇适合定性分析。我们的数据表明，对大脑中不同神经元进行光遗传学操作可以有效地挽救记忆障碍，减轻神经炎症，并减少阿尔茨海默病中的斑块病理。同样，这项技术对帕金森病运动症状和病理学中涉及基底神经节途径的各种神经元的贡献有了更深入的了解。然而，使用亨廷顿病、多发性硬化症和肌萎缩侧索硬化症动物模型的光遗传学应用受到限制。光遗传学是一种很有前途的技术，它增强了我们对神经退行性疾病研究的认识，并为治疗这些疾病的症状和延缓疾病进展提供了潜在的治疗方法。然而，应该考虑进行更先进的研究，以提高光遗传学工具的疗效和安全性，为其向临床转化铺平道路。
