Laboratory of Neurodegenerative Diseases, Universidad Autónoma de Chile, Chile.
Laboratorio de Función y Patología Neuronal, Departamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, 8331150 Santiago, Chile.
Redox Biol. 2018 Sep;18:279-294. doi: 10.1016/j.redox.2018.07.010. Epub 2018 Jul 19.
Tau is a key protein for microtubule stability; however, post-translationally modified tau contributes to neurodegenerative diseases by forming tau aggregates in the neurons. Previous reports from our group and others have shown that pathological forms of tau are toxic and impair mitochondrial function, whereas tau deletion is neuroprotective. However, the effects of tau ablation on brain structure and function in young mice have not been fully elucidated. Therefore, the aim of this study was to investigate the implications of tau ablation on the mitochondrial function and cognitive abilities of a litter of young mice (3 months old). Our results showed that tau deletion had positive effects on hippocampal cells by decreasing oxidative damage, favoring a mitochondrial pro-fusion state, and inhibiting mitochondrial permeability transition pore (mPTP) formation by reducing cyclophilin D (Cyp-D) protein. More importantly, tau deletion increased ATP production and improved the recognition memory and attentive capacity of juvenile mice. Therefore, the absence of tau enhanced brain function by improving mitochondrial health, which supplied more energy to the synapses. Thus, our work opens the possibility that preventing negative tau modifications could enhance brain function through the improvement of mitochondrial health.
tau 是微管稳定性的关键蛋白；然而，翻译后修饰的 tau 通过在神经元中形成 tau 聚集体导致神经退行性疾病。我们小组和其他小组的先前报告表明，病理性 tau 是有毒的，并损害线粒体功能，而 tau 的缺失具有神经保护作用。然而，tau 缺失对年轻小鼠大脑结构和功能的影响尚未完全阐明。因此，本研究旨在研究 tau 缺失对年轻小鼠（3 月龄）海马细胞线粒体功能和认知能力的影响。我们的研究结果表明，tau 缺失通过减少氧化损伤、促进线粒体融合状态以及通过减少亲环蛋白 D（Cyp-D）蛋白抑制线粒体通透性转换孔（mPTP）形成，对海马细胞产生了积极影响。更重要的是，tau 缺失增加了 ATP 的产生，并改善了幼年小鼠的识别记忆和注意力能力。因此，tau 的缺失通过改善线粒体健康增强了大脑功能，为突触提供了更多的能量。因此，我们的工作为通过改善线粒体健康来增强大脑功能提供了可能性。
