摘要
阿尔茨海默氏病(AD)是一种不可逆的神经退行性疾病,临床表现为记忆和认知的渐进性损伤。阿尔茨海默氏病的特征是神经原纤维缠结,主要通过改变磷酸化和截断的tau蛋白的部分构成的,与异常细胞外沉积具有神经毒性的β-淀粉样蛋白(Aβ)肽,由淀粉样前体蛋白(APP)的蛋白水解处理而来。根据淀粉样蛋白的假设,β-淀粉样蛋白是链接出现在阿尔茨海默氏病的视神经选择性神经退行性病变。最近的证据指出,钾电压增加(KV)通道发生在β-淀粉样蛋白诱导型的神经细胞凋亡的病因中 P物质(SP)是一个11个氨基酸的多肽,是速激肽家族的成员,广泛分布于中枢神经系统,它作为一种神经递质,神经递质和神经营养因子。这种肽可能在神经退行性疾病中发挥了重要的作用,因为P物质水平的减少被发现在阿尔茨海默氏病患者的脑区和脊髓液中。除了它的神经保护特性,最近表明,P物质能刺激非淀粉样淀粉样前体蛋白处理,从而减少大脑中的有毒β-淀粉样蛋白肽生成的可能性。最近的研究,在体外和体内模型中,也表明,P物质对β-淀粉样蛋白的保护作用,可能与它的调节钾电压通道电流的能力 在这篇综述中,我们简要地总结了当前的研究结果对P物质的神经营养和神经保护作用,提供有关其抗淀粉样蛋白和抗β-淀粉样蛋白毒性作用信息。
关键词: 阿尔茨海默病,抗淀粉样蛋白的活性,神经保护,P物质,速激肽,钾通道。
Current Alzheimer Research
Title:Substance P and Alzheimer’s Disease: Emerging Novel Roles
Volume: 13 Issue: 9
Author(s): Cinzia Severini, Carla Petrella, Pietro Calissano
Affiliation:
关键词: 阿尔茨海默病,抗淀粉样蛋白的活性,神经保护,P物质,速激肽,钾通道。
摘要: Alzheimer's disease (AD) is an irreversible neurodegenerative disease, clinically characterized by progressive impairments of memory and cognition. The hallmarks of AD are neurofibrillary tangles, mainly constituted by altered phosphorylated and truncated portions of tau protein, and the abnormal extracellular deposition of neurotoxic beta amyloid (Aβ) peptides, derived from the proteolytic processing of amyloid precursor protein (APP). According to the amyloid hypothesis, Aβ is considered to be linked to the selective neurodegeneration seen in AD. Recent evidence points to an increase in voltage-gated potassium (Kv) channel currents in the etiology of Aβ-induced neuronal apoptosis.
Substance P (SP) is an 11-aa neuropeptide, member of the tachykinin family, broadly distributed in the Central Nervous System where it acts as a neurotransmitter, neuromodulator, and neurotrophic factor. This peptide may play an important role in neurodegenerative disorders, since reduced levels of SP were found in brain areas and spinal fluid of AD patients. In addition to its neuroprotective properties, it was recently demonstrated that SP is able to stimulate non-amyloidogenic APP processing, thereby reducing the possibility of generation of toxic Aβ peptides in the brain. Recent studies, using in vitro and in vivo models, have also shown that the neuroprotective role of SP against Aβ could be related to its ability of modulate Kv channel currents.
In this review, we briefly summarized the current findings on the neurotrophic and neuroprotective effects of SP, providing information about its anti-amyloidogenic and anti-Aβ toxicity role.
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Cite this article as:
Cinzia Severini, Carla Petrella, Pietro Calissano , Substance P and Alzheimer’s Disease: Emerging Novel Roles, Current Alzheimer Research 2016; 13 (9) . https://dx.doi.org/10.2174/1567205013666160401114039
DOI https://dx.doi.org/10.2174/1567205013666160401114039 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
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