Duggan Michael R, Lu Anne, Foster Thomas C, Wimmer Mathieu, Parikh Vinay
Department of Psychology and Neuroscience Program, Temple University, Philadelphia, PA, United States.
Department of Neuroscience, University of Florida College of Medicine, Gainesville, FL, United States.
Front Aging Neurosci. 2022 Mar 1;14:834775. doi: 10.3389/fnagi.2022.834775. eCollection 2022.
Aging is the most prominent risk factor for cognitive decline, yet behavioral symptomology and underlying neurobiology can vary between individuals. Certain individuals exhibit significant age-related cognitive impairments, while others maintain intact cognitive functioning with only minimal decline. Recent developments in genomic, proteomic, and functional imaging approaches have provided insights into the molecular and cellular substrates of cognitive decline in age-related neuropathologies. Despite the emergence of novel tools, accurately and reliably predicting longitudinal cognitive trajectories and improving functional outcomes for the elderly remains a major challenge. One promising approach has been the use of exosomes, a subgroup of extracellular vesicles that regulate intercellular communication and are easily accessible compared to other approaches. In the current review, we highlight recent findings which illustrate how the analysis of exosomes can improve our understanding of the underlying neurobiological mechanisms that contribute to cognitive variation in aging. Specifically, we focus on exosome-mediated regulation of miRNAs, neuroinflammation, and aggregate-prone proteins. In addition, we discuss how exosomes might be used to enhance individual patient outcomes by serving as reliable biomarkers of cognitive decline and as nanocarriers to deliver therapeutic agents to the brain in neurodegenerative conditions.
衰老是认知衰退最显著的风险因素，但个体之间的行为症状学和潜在神经生物学可能存在差异。某些个体表现出明显的与年龄相关的认知障碍，而另一些人则仅出现轻微衰退，仍保持完整的认知功能。基因组学、蛋白质组学和功能成像方法的最新进展为与年龄相关的神经病理学中认知衰退的分子和细胞基础提供了见解。尽管出现了新工具，但准确可靠地预测老年人的纵向认知轨迹并改善其功能结局仍然是一项重大挑战。一种有前景的方法是使用外泌体，这是细胞外囊泡的一个亚群，可调节细胞间通讯，与其他方法相比更容易获取。在本综述中，我们重点介绍了最近的研究结果，这些结果说明了外泌体分析如何能增进我们对导致衰老过程中认知差异的潜在神经生物学机制的理解。具体而言，我们关注外泌体介导的微小RNA、神经炎症和易聚集蛋白的调控。此外，我们还讨论了外泌体如何通过作为认知衰退的可靠生物标志物以及作为在神经退行性疾病中将治疗药物输送到大脑的纳米载体，来改善个体患者的预后。
