钙信号传导与神经退行性疾病
Calcium signaling and neurodegenerative diseases.
作者信息
Bezprozvanny Ilya
机构信息
Department of Physiology, UT Southwestern Medical Center at Dallas, Dallas, TX 75390-9040, USA.
出版信息
Trends Mol Med. 2009 Mar;15(3):89-100. doi: 10.1016/j.molmed.2009.01.001. Epub 2009 Feb 21.
Abstract
Neurodegenerative disorders, such as Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), Huntington's disease (HD) and spinocerebellar ataxias (SCAs), present an enormous medical, social, financial and scientific problem. Recent evidence indicates that neuronal calcium (Ca2+) signaling is abnormal in many of these disorders. Similar, but less severe, changes in neuronal Ca2+ signaling occur as a result of the normal aging process. The role of aberrant neuronal Ca2+ signaling in the pathogenesis of neurodegenerative disorders is discussed here. The potential utility of Ca2+ blockers for treatment of these disorders is also highlighted. It is reasoned that Ca2+ blockers will be most beneficial clinically when used in combination with other disease-specific therapeutic approaches.
摘要
神经退行性疾病，如阿尔茨海默病（AD）、帕金森病（PD）、肌萎缩侧索硬化症（ALS）、亨廷顿病（HD）和脊髓小脑共济失调（SCA），带来了巨大的医学、社会、经济和科学问题。最近的证据表明，在许多这类疾病中神经元钙（Ca2+）信号是异常的。由于正常衰老过程，神经元Ca2+信号也会出现类似但不太严重的变化。本文讨论了异常神经元Ca2+信号在神经退行性疾病发病机制中的作用。还强调了Ca2+阻滞剂对治疗这些疾病的潜在效用。据推断，Ca2+阻滞剂与其他针对特定疾病的治疗方法联合使用时，在临床上将最为有益。
相似文献
1
Calcium signaling and neurodegenerative diseases.钙信号传导与神经退行性疾病
Trends Mol Med. 2009 Mar;15(3):89-100. doi: 10.1016/j.molmed.2009.01.001. Epub 2009 Feb 21.
2
SERCA pump as a novel therapeutic target for treating neurodegenerative disorders.肌浆网 Ca2+-ATP 酶作为治疗神经退行性疾病的新治疗靶点。
Biochem Biophys Res Commun. 2024 Nov 19;734:150748. doi: 10.1016/j.bbrc.2024.150748. Epub 2024 Sep 26.
3
Calcium signaling and molecular mechanisms underlying neurodegenerative diseases.钙信号与神经退行性疾病的分子机制。
Cell Calcium. 2018 Mar;70:87-94. doi: 10.1016/j.ceca.2017.06.008. Epub 2017 Jun 30.
4
Targeting TRPs in neurodegenerative disorders.靶向神经退行性疾病中的 TRP 通道。
Curr Top Med Chem. 2013;13(3):322-34. doi: 10.2174/1568026611313030009.
5
Calcium signaling and neurodegeneration.钙信号与神经退行性变。
Acta Naturae. 2010 Apr;2(1):72-82.
6
Disturbed calcium signaling in spinocerebellar ataxias and Alzheimer's disease.脊髓小脑共济失调和阿尔茨海默病中钙信号传导紊乱。
Semin Cell Dev Biol. 2015 Apr;40:127-33. doi: 10.1016/j.semcdb.2015.03.010. Epub 2015 Apr 4.
7
Role of connexins in neurodegenerative diseases (Review).连接蛋白在神经退行性疾病中的作用（综述）
Mol Med Rep. 2021 May;23(5). doi: 10.3892/mmr.2021.12034. Epub 2021 Mar 24.
8
Oxidative stress, mitochondrial dysfunction and cellular stress response in Friedreich's ataxia.弗里德赖希共济失调中的氧化应激、线粒体功能障碍和细胞应激反应
J Neurol Sci. 2005 Jun 15;233(1-2):145-62. doi: 10.1016/j.jns.2005.03.012.
9
Metal-catalyzed disruption of membrane protein and lipid signaling in the pathogenesis of neurodegenerative disorders.金属催化的膜蛋白和脂质信号紊乱在神经退行性疾病发病机制中的作用
Ann N Y Acad Sci. 2004 Mar;1012:37-50. doi: 10.1196/annals.1306.004.
10
Astrocytes in neurodegenerative disease.神经退行性疾病中的星形胶质细胞。
Cold Spring Harb Perspect Biol. 2015 Apr 15;7(6):a020628. doi: 10.1101/cshperspect.a020628.
引用本文的文献
1
Spatiotemporal Dynamics of Central Nervous System Diseases: Advancing Translational Neuropathology via Single-Cell and Spatial Multiomics.中枢神经系统疾病的时空动态：通过单细胞和空间多组学推进转化神经病理学
MedComm (2020). 2025 Aug 19;6(9):e70328. doi: 10.1002/mco2.70328. eCollection 2025 Sep.
2
Electrical silencing of dendritic arborization neurons rescues toxic polyglutamine-induced locomotion defect.树突状分支神经元的电沉默可挽救有毒多聚谷氨酰胺诱导的运动缺陷。
Fly (Austin). 2025 Dec;19(1):2519687. doi: 10.1080/19336934.2025.2519687. Epub 2025 Jun 16.
3
Impairment of Tricarboxylic Acid Cycle (TCA) Cycle in Alzheimer's Disease: Mechanisms, Implications, and Potential Therapies.阿尔茨海默病中三羧酸循环（TCA循环）的损伤：机制、影响及潜在治疗方法
Aging Dis. 2025 May 29;16(5):2553-2574. doi: 10.14336/AD.2025.0472.
4
Development of a Japanese polygenic risk score model for amyloid-β PET imaging in Alzheimer's disease.用于阿尔茨海默病淀粉样蛋白β正电子发射断层显像的日本多基因风险评分模型的开发。
Alzheimers Res Ther. 2025 May 22;17(1):112. doi: 10.1186/s13195-025-01754-2.
5
Brain proteome changes after intracerebral hemorrhage in aged male and female mice.老年雄性和雌性小鼠脑出血后的脑蛋白质组变化
Neurobiol Dis. 2025 Aug;212:106936. doi: 10.1016/j.nbd.2025.106936. Epub 2025 May 2.
6
The motor neuron m6A repertoire governs neuronal homeostasis and FTO inhibition mitigates ALS symptom manifestation.运动神经元的m6A图谱调控神经元稳态，FTO抑制可减轻肌萎缩侧索硬化症症状表现。
Nat Commun. 2025 Apr 30;16(1):4063. doi: 10.1038/s41467-025-59117-2.
7
Pathway-based network medicine identifies novel natural products for Alzheimer's disease.基于通路的网络医学识别出用于治疗阿尔茨海默病的新型天然产物。
Alzheimers Res Ther. 2025 Feb 14;17(1):43. doi: 10.1186/s13195-025-01694-x.
8
A fuzzy based computational model to analyze the influence of mitochondria, buffer, and ER fluxes on cytosolic calcium distribution in neuron cells.一种基于模糊逻辑的计算模型，用于分析线粒体、缓冲液和内质网通量对神经元细胞胞质钙分布的影响。
Cogn Neurodyn. 2025 Dec;19(1):25. doi: 10.1007/s11571-024-10212-y. Epub 2025 Jan 13.
9
Calcium Signalling in Neurological Disorders, with Insights from Miniature Fluorescence Microscopy.基于微型荧光显微镜技术对神经疾病中钙信号传导的见解
Cells. 2024 Dec 25;14(1):4. doi: 10.3390/cells14010004.
10
Calcium oscillations and mitochondrial enzymes in stem cells.干细胞中的钙振荡与线粒体酶
Regen Ther. 2024 Sep 14;26:811-818. doi: 10.1016/j.reth.2024.09.002. eCollection 2024 Jun.
本文引用的文献
1
Neuroprotective effects of inositol 1,4,5-trisphosphate receptor C-terminal fragment in a Huntington's disease mouse model.1,4,5-三磷酸肌醇受体C末端片段在亨廷顿病小鼠模型中的神经保护作用
J Neurosci. 2009 Feb 4;29(5):1257-66. doi: 10.1523/JNEUROSCI.4411-08.2009.
2
Mitochondrial approaches for neuroprotection.用于神经保护的线粒体方法。
Ann N Y Acad Sci. 2008 Dec;1147:395-412. doi: 10.1196/annals.1427.027.
3
No association between CALHM1 and Alzheimer's disease risk.CALHM1与阿尔茨海默病风险之间无关联。
Cell. 2008 Dec 12;135(6):993-4; author reply 994-6. doi: 10.1016/j.cell.2008.11.030.
4
Polyglutamine-modulated striatal calpain activity in YAC transgenic huntington disease mouse model: impact on NMDA receptor function and toxicity.聚谷氨酰胺调节的YAC转基因亨廷顿病小鼠模型纹状体钙蛋白酶活性：对NMDA受体功能和毒性的影响
J Neurosci. 2008 Nov 26;28(48):12725-35. doi: 10.1523/JNEUROSCI.4619-08.2008.
5
Deranged calcium signaling and neurodegeneration in spinocerebellar ataxia type 3.脊髓小脑共济失调3型中钙信号紊乱与神经退行性变
J Neurosci. 2008 Nov 26;28(48):12713-24. doi: 10.1523/JNEUROSCI.3909-08.2008.
6
Mutant huntingtin and mitochondrial dysfunction.突变型亨廷顿蛋白与线粒体功能障碍
Trends Neurosci. 2008 Dec;31(12):609-16. doi: 10.1016/j.tins.2008.09.004. Epub 2008 Oct 24.
7
Evaluation of Dimebon in cellular model of Huntington's disease.评价 dimebon 在亨廷顿病细胞模型中的作用。
Mol Neurodegener. 2008 Oct 21;3:15. doi: 10.1186/1750-1326-3-15.
8
Inhibitors of cytochrome c release with therapeutic potential for Huntington's disease.具有治疗亨廷顿舞蹈症潜力的细胞色素c释放抑制剂。
J Neurosci. 2008 Sep 17;28(38):9473-85. doi: 10.1523/JNEUROSCI.1867-08.2008.
9
Spinocerebellar ataxia type 6 knockin mice develop a progressive neuronal dysfunction with age-dependent accumulation of mutant CaV2.1 channels.6型脊髓小脑共济失调基因敲入小鼠随着年龄增长，突变型CaV2.1通道逐渐积累，从而出现进行性神经元功能障碍。
Proc Natl Acad Sci U S A. 2008 Aug 19;105(33):11987-92. doi: 10.1073/pnas.0804350105. Epub 2008 Aug 7.
10
Calpain-mediated signaling mechanisms in neuronal injury and neurodegeneration.钙蛋白酶介导的神经元损伤和神经退行性变中的信号传导机制。
Mol Neurobiol. 2008 Aug;38(1):78-100. doi: 10.1007/s12035-008-8036-x. Epub 2008 Aug 7.
Zotero 插件