Inorganic Polyphosphate, Mitochondria, and Neurodegeneration.
Inorganic Polyphosphate, Mitochondria, and Neurodegeneration.
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无机多磷酸盐、线粒体和神经变性。
DOI：
10.1007/978-3-031-01237-2_3
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发表时间：
2022
影响因子：
--
通讯作者：
Solesio,MariaE
中科院分区：
文献类型：
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作者：
Urquiza,Pedro;Solesio,MariaE
随着人口老龄化，预计在未来几十年内，与衰老相关的病理学的存在将增加。遗憾的是，我们仍然没有任何有效的药理学或非药理学工具来预防、逆转或治愈这些病理。对衰老相关的病理学缺乏治疗方法至少可以部分解释为我们仍然缺乏关于其分子机制的知识，以及其发病机制的复杂性。事实上，在所有这些与衰老相关的病理学中，包括神经退行性疾病，都描述了细胞生理功能的复杂变化。基于我们和其他人制作的多个科学手稿，似乎很明显，线粒体在许多与衰老相关的病理中功能失调。例如，线粒体功能障碍是所有主要神经退行性疾病的病因学中的早期事件，并且它可能是这些病理中存在于细胞水平的许多其他有害变化的触发因素。虽然线粒体是复杂的细胞器，它们的调节仍然没有完全理解，但无机多磷酸盐（polyP）可能在调节一些线粒体过程中发挥关键作用，这些过程在神经变性中功能失调。PolyP是一种保存完好的生物聚合物;它已在已研究的每种生物体中被发现。它由一系列正磷酸盐组成，这些正磷酸盐通过高能磷酸酐键连接，与ATP中发现的正磷酸盐相当。文献表明，聚P在维持线粒体生理学中的作用可能至少部分地与其作为细胞生物能量学的关键调节剂的作用有关。然而，需要进行进一步的研究，以充分阐明polyP在衰老相关病理学（包括神经退行性疾病）中调节线粒体生理学作用的分子机制。由于显著缺乏用于预防和/或治疗神经变性的治疗选择，在过去几十年中一直在寻找针对这些病症的新药理学工具，尽管很少有治疗方法显示出治疗这些病理的潜力。因此，增加我们对polyP在线粒体生理学及其代谢中的作用的分子机制的了解，可以将这种聚合物作为一个有前途的和创新的药理学靶标，不仅在神经变性中，而且在广泛的衰老相关的病理学和病症中，其中线粒体功能障碍被描述为其病因学的关键组成部分，如糖尿病，肌肉骨骼疾病，和心血管疾病。
With an aging population, the presence of aging-associated pathologies is expected to increase within the next decades. Regrettably, we still do not have any valid pharmacological or non-pharmacological tools to prevent, revert, or cure these pathologies. The absence of therapeutical approaches against aging-associated pathologies can be at least partially explained by the relatively lack of knowledge that we still have regarding the molecular mechanisms underlying them, as well as by the complexity of their etiopathology. In fact, a complex number of changes in the physiological function of the cell has been described in all these aging-associated pathologies, including neurodegenerative disorders. Based on multiple scientific manuscripts produced by us and others, it seems clear that mitochondria are dysfunctional in many of these aging-associated pathologies. For example, mitochondrial dysfunction is an early event in the etiopathology of all the main neurodegenerative disorders, and it could be a trigger of many of the other deleterious changes which are present at the cellular level in these pathologies. While mitochondria are complex organelles and their regulation is still not yet entirely understood, inorganic polyphosphate (polyP) could play a crucial role in the regulation of some mitochondrial processes, which are dysfunctional in neurodegeneration. PolyP is a well-preserved biopolymer; it has been identified in every organism that has been studied. It is constituted by a series of orthophosphates connected by highly energetic phosphoanhydride bonds, comparable to those found in ATP. The literature suggests that the role of polyP in maintaining mitochondrial physiology might be related, at least partially, to its effects as a key regulator of cellular bioenergetics. However, further research needs to be conducted to fully elucidate the molecular mechanisms underlying the effects of polyP in the regulation of mitochondrial physiology in aging-associated pathologies, including neurodegenerative disorders. With a significant lack of therapeutic options for the prevention and/or treatment of neurodegeneration, the search for new pharmacological tools against these conditions has been continuous in past decades, even though very few therapeutic approaches have shown potential in treating these pathologies. Therefore, increasing our knowledge about the molecular mechanisms underlying the effects of polyP in mitochondrial physiology as well as its metabolism could place this polymer as a promising and innovative pharmacological target not only in neurodegeneration, but also in a wide range of aging-associated pathologies and conditions where mitochondrial dysfunction has been described as a crucial component of its etiopathology, such as diabetes, musculoskeletal disorders, and cardiovascular disorders.