Center of Emphasis in Neuroscience, Department of Molecular and Translational Medicine, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, TX 79905, USA.
Department of Veterinary Pathobiology and Bond Life Sciences Center, University of Missouri, 1201 Rollins Street, Columbia, MO 65211, USA.
Cells. 2023 Feb 25;12(5):742. doi: 10.3390/cells12050742.
Mitochondria play several vital roles in the brain cells, especially in neurons to provide synaptic energy (ATP), Ca homeostasis, Reactive Oxygen Species (ROS) production, apoptosis, mitophagy, axonal transport and neurotransmission. Mitochondrial dysfunction is a well-established phenomenon in the pathophysiology of many neurological diseases, including Alzheimer's disease (AD). Amyloid-beta (Aβ) and Phosphorylated tau (p-tau) proteins cause the severe mitochondrial defects in AD. A newly discovered cellular niche of microRNAs (miRNAs), so-called mitochondrial-miRNAs (mito-miRs), has recently been explored in mitochondrial functions, cellular processes and in a few human diseases. The mitochondria localized miRNAs regulate local mitochondrial genes expression and are significantly involved in the modulation of mitochondrial proteins, and thereby in controlling mitochondrial function. Thus, mitochondrial miRNAs are crucial to maintaining mitochondrial integrity and for normal mitochondrial homeostasis. Mitochondrial dysfunction is well established in AD pathogenesis, but unfortunately mitochondria miRNAs and their precise roles have not yet been investigated in AD. Therefore, an urgent need exists to examine and decipher the critical roles of mitochondrial miRNAs in AD and in the aging process. The current perspective sheds light on the latest insights and future research directions on investigating the contribution of mitochondrial miRNAs in AD and aging.
线粒体在脑细胞中发挥着多种重要作用，特别是在神经元中提供突触能量（ATP）、钙稳态、活性氧物种（ROS）产生、细胞凋亡、线粒体自噬、轴突运输和神经递质传递。线粒体功能障碍是许多神经疾病病理生理学中的一个既定现象，包括阿尔茨海默病（AD）。淀粉样蛋白-β（Aβ）和磷酸化tau（p-tau）蛋白导致 AD 中严重的线粒体缺陷。最近，人们在研究线粒体功能、细胞过程以及一些人类疾病时，发现了一个新的细胞微 RNA（miRNA）细胞生态位，即所谓的线粒体微 RNA（mito-miRs）。位于线粒体的 miRNAs 调节局部线粒体基因的表达，并且显著参与线粒体蛋白的调节，从而控制线粒体功能。因此，线粒体 miRNAs 对于维持线粒体的完整性和正常的线粒体稳态至关重要。线粒体功能障碍在 AD 的发病机制中已得到充分证实，但不幸的是，miRNAs 在 AD 中的作用及其确切作用尚未得到研究。因此，迫切需要研究和阐明线粒体 miRNAs 在 AD 及衰老过程中的关键作用。目前的观点阐明了最新的研究进展和未来研究方向，即研究线粒体 miRNAs 在 AD 和衰老中的作用。
