Cardiolipin, Mitochondria, and Neurological Disease.
Cardiolipin, Mitochondria, and Neurological Disease.
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DOI：
10.1016/j.tem.2021.01.006
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发表时间：
2021-04
期刊：
影响因子：
--
通讯作者：
Pitceathly RDS
中科院分区：
文献类型：
--
作者：
Falabella M;Vernon HJ;Hanna MG;Claypool SM;Pitceathly RDS
在过去的十年中，人们已经清楚，脂质稳态是细胞代谢的核心。脂质在中枢神经系统（CNS）中特别丰富，在中枢神经系统中它们调节膜流动性、电信号转导和突触稳定。阿尔茨海默病（AD）、帕金森病（PD）、肌萎缩侧索硬化症（ALS）和创伤性脑损伤（TBI）中报告的异常脂质谱进一步支持脂质代谢在神经系统中的重要性。心磷脂（CL）是一种仅存在于大脑中的磷脂，近年来已成为神经退行性疾病研究的热点。异常的CL含量、结构和定位与受损的神经发生和神经元功能障碍有关，有助于衰老和几种神经退行性疾病（如AD和PD）的发病机制。此外，CL的高度组织特异性酰基链组成赋予其作为生物标志物诊断和监测几种神经系统疾病进展的显著潜力。CL也代表了旨在治疗神经变性的药理学策略的潜在靶标。鉴于平衡，目前存在的CL代谢，线粒体功能和神经系统疾病之间，我们审查CL在神经系统生理学和单基因和神经退行性疾病的病理生理学的作用，除了其作为生物标志物和药理学靶点的潜在应用。中枢神经系统富含支持膜流动性、电信号转导和突触稳定的脂质。心磷脂（CL）是一种对线粒体形态、生物能量学、动力学和信号传导途径至关重要的磷脂。脑CL的改变与神经元功能受损和神经变性相关。CL的高度组织特异性酰基链组成赋予其作为生物标志物诊断和监测几种神经系统疾病的进展的显着潜力。CL代表了旨在治疗神经变性的药理学策略的潜在靶标。
Over the past decade, it has become clear that lipid homeostasis is central to cellular metabolism. Lipids are particularly abundant in the central nervous system (CNS) where they modulate membrane fluidity, electric signal transduction, and synaptic stabilization. Abnormal lipid profiles reported in Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), and traumatic brain injury (TBI), are further support for the importance of lipid metablism in the nervous system. Cardiolipin (CL), a mitochondria-exclusive phospholipid, has recently emerged as a focus of neurodegenerative disease research. Aberrant CL content, structure, and localization are linked to impaired neurogenesis and neuronal dysfunction, contributing to aging and the pathogenesis of several neurodegenerative diseases, such as AD and PD. Furthermore, the highly tissue-specific acyl chain composition of CL confers it significant potential as a biomarker to diagnose and monitor the progression in several neurological diseases. CL also represents a potential target for pharmacological strategies aimed at treating neurodegeneration. Given the equipoise that currently exists between CL metabolism, mitochondrial function, and neurological disease, we review the role of CL in nervous system physiology and monogenic and neurodegenerative disease pathophysiology, in addition to its potential application as a biomarker and pharmacological target. The central nervous system is rich in lipids that support membrane fluidity, electric signal transduction, and synaptic stabilization. Cardiolipin (CL) is a mitochondria-exclusive phospholipid essential for mitochondrial morphology, bioenergetics, dynamics, and signaling pathways. Alterations in brain CL are associated with impaired neuronal function and neurodegeneration. The highly tissue-specific acyl chain composition of CL confers it significant potential as a biomarker to diagnose and monitor the progression in several neurological diseases. CL represents a potential target for pharmacological strategies aimed at treating neurodegeneration.
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影响因子：
7.4
作者：
Baxter, Paul S.;Hardingham, Giles E.
通讯作者：
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影响因子：
4.8
作者：
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影响因子：
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影响因子：
30.8
作者：
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通讯作者：
Toniolo, D
影响因子：
5.3
作者：
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通讯作者：
Ji, Jing