Calvo Belén, Schembri-Wismayer Pierre, Durán-Alonso María Beatriz
Faculty of Health Sciences, Catholic University of Ávila, 05005 Ávila, Spain.
Department of Anatomy, Faculty of Medicine and Surgery, University of Malta, MSD 2080 Msida, Malta.
Cells. 2025 Feb 27;14(5):347. doi: 10.3390/cells14050347.
Neurodegenerative diseases encompass a number of very heterogeneous disorders, primarily characterized by neuronal loss and a concomitant decline in neurological function. Examples of this type of clinical condition are Alzheimer's Disease, Parkinson's Disease, Huntington's Disease and Amyotrophic Lateral Sclerosis. Age has been identified as a major risk in the etiology of these disorders, which explains their increased incidence in developed countries. Unfortunately, despite continued and intensive efforts, no cure has yet been found for any of these diseases; reliable markers that allow for an early diagnosis of the disease and the identification of key molecular events leading to disease onset and progression are lacking. Altered adult neurogenesis appears to precede the appearance of severe symptoms. Given the scarcity of human samples and the considerable differences with model species, increasingly complex human stem-cell-based models are being developed. These are shedding light on the molecular alterations that contribute to disease development, facilitating the identification of new clinical targets and providing a screening platform for the testing of candidate drugs. Moreover, the secretome and other promising features of these cell types are being explored, to use them as replacement cells of high plasticity or as co-adjuvant therapy in combinatorial treatments.
神经退行性疾病包括许多非常异质性的疾病,主要特征是神经元丢失以及随之而来的神经功能衰退。这类临床病症的例子有阿尔茨海默病、帕金森病、亨廷顿病和肌萎缩侧索硬化症。年龄已被确定为这些疾病病因中的主要风险因素,这解释了它们在发达国家发病率上升的原因。不幸的是,尽管持续进行了深入努力,但尚未找到治愈这些疾病的方法;缺乏能够实现疾病早期诊断以及识别导致疾病发生和进展的关键分子事件的可靠标志物。成人神经发生改变似乎先于严重症状出现。鉴于人类样本稀缺且与模式物种存在相当大的差异,越来越复杂的基于人类干细胞的模型正在被开发出来。这些模型正在揭示促成疾病发展的分子改变,有助于识别新的临床靶点,并为候选药物测试提供筛选平台。此外,正在探索这些细胞类型的分泌组和其他有前景的特性,以便将它们用作高可塑性的替代细胞或在联合治疗中用作辅助治疗。