Vaiasicca Salvatore, Balietti Marta, Bevilacqua Lisa, Giorgetti Belinda, Casoli Tiziana
Scientific Direction, IRCCS INRCA, Ancona 60124, Italy.
Center for Neurobiology of Aging, IRCCS INRCA, Ancona 60121, Italy.
Mech Ageing Dev. 2024 Dec;222:112001. doi: 10.1016/j.mad.2024.112001. Epub 2024 Oct 28.
Alzheimer's disease (AD) accounts for the majority of dementia cases, with aging being the primary risk factor for developing this neurodegenerative condition. Aging and AD share several characteristics, including the formation of amyloid plaques and neurofibrillary tangles, synaptic loss, and neuroinflammation. This overlap suggests that mechanisms driving the aging process might also promote AD; however, the underlying processes are not yet fully understood. In this narrative review, we will focus on the role of mitochondria, not only as the "powerhouse of the cell", but also in programmed cell death, immune response, macromolecular synthesis, and calcium regulation. We will explore both the common changes between aging and AD and the differences between them. Additionally, we will provide an overview of interventions aimed at maintaining mitochondrial function in an attempt to slow the progression of AD. This will include a discussion of antioxidant molecules, factors that trigger mitochondrial biogenesis, compounds capable of restoring the fission/fusion balance, and a particular focus on recent techniques for mitochondrial DNA gene therapy.
阿尔茨海默病(AD)占痴呆症病例的大多数,衰老为这种神经退行性疾病的主要风险因素。衰老和AD具有若干共同特征,包括淀粉样斑块和神经原纤维缠结的形成、突触丧失和神经炎症。这种重叠表明,驱动衰老过程的机制可能也会促进AD;然而,其潜在过程尚未完全了解。在这篇叙述性综述中,我们将聚焦线粒体的作用,其不仅作为“细胞的动力源”,而且在程序性细胞死亡、免疫反应、大分子合成及钙调节方面也发挥作用。我们将探讨衰老与AD之间的共同变化以及二者之间的差异。此外,我们将概述旨在维持线粒体功能以减缓AD进展的干预措施。这将包括对抗氧化分子、触发线粒体生物发生的因素、能够恢复裂变/融合平衡的化合物的讨论,特别关注线粒体DNA基因治疗的最新技术。