Department of Food Science and Nutrition, Nara Women's University, Kita-Uoya Nishimachi, Nara 630-8506, Japan.
Molecules. 2024 Aug 20;29(16):3922. doi: 10.3390/molecules29163922.
Some neurodegenerative diseases may be characterized by continuing behavioral and cognitive dysfunction that encompasses memory loss and/or apathy. Alzheimer's disease is the most typical type of such neurodegenerative diseases that are characterized by deficits of cognition and alterations of behavior. Despite the huge efforts against Alzheimer's disease, there has yet been no successful treatment for this disease. Interestingly, several possible risk genes for cognitive dysfunction are frequently expressed within brain cells, which may also be linked to cholesterol metabolism, lipid transport, exosomes, and/or caveolae formation, suggesting that caveolae may be a therapeutic target for cognitive dysfunctions. Interestingly, the modulation of autophagy/mitophagy with the alteration of glucagon-like peptide-1 (GLP-1) and N-methyl-d-aspartate (NMDA) receptor signaling may offer a novel approach to preventing and alleviating cognitive dysfunction. A paradigm showing that both GLP-1 and NMDA receptors at caveolae sites may be promising and crucial targets for the treatment of cognitive dysfunctions has been presented here, which may also be able to modify the progression of Alzheimer's disease. This research direction may create the potential to move clinical care toward disease-modifying treatment strategies with maximal benefits for patients without detrimental adverse events for neurodegenerative diseases.
一些神经退行性疾病的特征可能是持续的行为和认知功能障碍，包括记忆丧失和/或冷漠。阿尔茨海默病是最典型的神经退行性疾病，其特征是认知缺陷和行为改变。尽管针对阿尔茨海默病进行了巨大的努力，但这种疾病仍然没有有效的治疗方法。有趣的是，几个可能导致认知功能障碍的风险基因经常在脑细胞内表达，这些基因也可能与胆固醇代谢、脂质转运、外泌体和/或 caveolae 形成有关，这表明 caveolae 可能是治疗认知功能障碍的一个靶点。有趣的是，通过改变胰高血糖素样肽-1（GLP-1）和 N-甲基-D-天冬氨酸（NMDA）受体信号来调节自噬/线粒体自噬，可能为预防和缓解认知功能障碍提供一种新的方法。本文提出了一个模型，表明 caveolae 部位的 GLP-1 和 NMDA 受体都可能是治疗认知功能障碍的有前途和关键靶点，也可能能够改变阿尔茨海默病的进展。这一研究方向可能为临床治疗提供潜力，使治疗策略朝着具有最大益处的疾病修正治疗方向发展，而不会对神经退行性疾病产生有害的不良反应。
