Role of the Sigma-1 receptor in Amyotrophic Lateral Sclerosis (ALS).
Role of the Sigma-1 receptor in Amyotrophic Lateral Sclerosis (ALS).
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DOI：
10.1016/j.jphs.2014.12.013
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发表时间：
2015-01
影响因子：
3.5
通讯作者：
Ruoho, Arnold E.
中科院分区：
文献类型：
--
作者：
Mavlyutov, Timur A.;Guo, Lian-Wang;Epstein, Miles L.;Ruoho, Arnold E.
肌萎缩侧索硬化症(ALS)是一种影响脊髓运动神经元(MN)的神经退行性疾病，与额颞叶痴呆(FTLD)有关。内质网(ER)结合的Sigma-1受体(S1R)伴侣蛋白定位于脊髓腹角胆碱能突触后C终末胞膜10 nm以内的特化ER池。在ALS的超氧化物歧化酶-1(SOD-1)小鼠模型中，S1R基因的移除加剧了神经退行性疾病，并导致与SOD-1/S1R野生型(WT)小鼠相比，寿命显著降低。与S1R KO小鼠MN相比，S1R对ALS表型的改善可能是由于对MN的刺激被“刹车”所致，WT的MN的动作电位产生减少就是证据。虽然MN中S1R调控的确切信号转导途径(S)目前还不清楚，但内质网池中的S1R可能与电压门控钾通道和/或突触后质膜上的M_2受体信号发生直接或间接的功能相互作用。讨论了S1R调节MN兴奋性的可能机制。
Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease affecting spinal cord motoneurons (MN) with an associative connection to Frontotemporal Lobar Dementia (FTLD). The endoplasmic reticulum (ER) bound Sigma-1 Receptor (S1R) chaperone protein localizes to specialized ER cisternae within 10 nm of the plasma membrane in spinal cord ventral horn cholinergic post synaptic C-terminals. Removal of the S1R gene in the Superoxide Dismutase-1 (SOD-1) mouse model of ALS exacerbated the neurodegenerative condition and resulted in a significantly reduced longevity when compared to the SOD-1/S1R wild type (WT) mouse. The proposed amelioration of the ALS phenotype by the S1R is likely due to a “brake” on excitation of the MN as evidenced by a reduction in action potential generation in the MN of the WT when compared to the S1R KO mouse MN. Although the precise signal transduction pathway(s) regulated by the S1R in the MN has/have not been elucidated at present, it is likely that direct or indirect functional interactions occur between the S1R in the ER cisternae with voltage gated potassium channels and/or with muscarinic M2 receptor signaling in the post synaptic plasma membrane. Possible mechanisms for regulation of MN excitability by S1R are discussed.
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DOI：
10.1126/science.1166127
发表时间：
2009-02-13
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Fontanilla D;Johannessen M;Hajipour AR;Cozzi NV;Jackson MB;Ruoho AE
通讯作者：
Ruoho AE
影响因子：
2.3
作者：
Fujimoto, Michiko;Hayashi, Teruo;Urfer, Roman;Mita, Shiro;Su, Tsung-Ping
通讯作者：
Su, Tsung-Ping
影响因子：
2.1
作者：
Ajmo, Craig T., Jr.;Vernon, Dionne O. L.;Cuevas, Javier
通讯作者：
Cuevas, Javier
影响因子：
3.9
作者：
Abel, Olubunmi;Powell, John F.;Al-Chalabi, Ammar
通讯作者：
Al-Chalabi, Ammar
影响因子：
3.1
作者：
Casas, Caty;Herrando-Grabulosa, Mireia;Navarro, Xavier
通讯作者：
Navarro, Xavier