Role of neurotrophic factor alterations in the neurodegenerative process in HIV associated neurocognitive disorders.
Role of neurotrophic factor alterations in the neurodegenerative process in HIV associated neurocognitive disorders.
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DOI：
10.1007/s11481-013-9520-2
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发表时间：
2014-03
影响因子：
6.2
通讯作者：
Masliah, E.
中科院分区：
文献类型：
--
作者：
Fields, Jerel;Dumaop, Wilmar;Langford, T. D.;Rockenstein, Edward;Masliah, E.
关键词：
HIV感染细胞迁移到CNS与一系列神经系统疾病相关，从较轻度的HIV相关神经认知障碍（HAND）到HIV相关痴呆（HAD）。这些神经精神综合征与由HIV蛋白和细胞因子/趋化因子从单核细胞/巨噬细胞释放到CNS中触发的神经退行性病理学相关-一种称为HIV脑炎（HIVE）的病症。由于更有效的联合抗逆转录病毒治疗（cART），艾滋病毒患者的寿命更长，因此HAND的频率大大增加，导致与艾滋病毒相关的神经退行性病变与衰老相关的神经退行性病变重叠。事实上，艾滋病毒感染被认为会加速衰老过程。HIV和衰老导致神经退行性变的机制包括：异常钙流、兴奋性毒性、信号异常、氧化应激和自噬缺陷。此外，最近的研究表明，神经营养因子如成纤维细胞生长因子（FGF），神经生长因子（NGF）和脑源性生长因子（BDNF）的加工和运输缺陷也可能发挥作用。最近的证据表明神经营养因子的改变在衰老背景下与HAND相关的神经变性的发病机制中起作用。在这里，我们报告FGF过表达削减gp 120诱导的神经毒性在双转基因小鼠模型。此外，我们的数据显示，脑神经营养因子水平的差异可能在50岁以上的艾滋病毒患者中加剧。在这篇综述中，我们讨论了神经营养因子和手的背景下，开发新的治疗方法，以打击艾滋病毒感染的老龄化人口的最新研究结果。
Migration of HIV infected cells into the CNS is associated with a spectrum of neurological disorders, ranging from milder forms of HIV-associated neurocognitive disorders (HAND) to HIV-associated dementia (HAD). These neuro-psychiatric syndromes are related to the neurodegenerative pathology triggered by the release of HIV proteins and cytokine/chemokines from monocytes/macrophages into the CNS –a condition known as HIV encephalitis (HIVE). As a result of more effective combined anti-retroviral therapy (cART) patients with HIV are living longer and thus the frequency of HAND has increased considerably, resulting in an overlap between the neurodegenerative pathology associated with HIV and that related to aging. In fact, HIV infection is believed to hasten the aging process. The mechanisms through which HIV and aging lead to neurodegeneration include: abnormal calcium flux, excitotoxicity, signaling abnormalities, oxidative stress and autophagy defects. Moreover, recent studies have shown that defects in the processing and transport of neurotrophic factors such as fibroblast growth factors (FGFs), neural growth factor (NGF) and brain-derived growth factor (BDNF) might also play a role. Recent evidence implicates alterations in neurotrophins in the pathogenesis of neurodegeneration associated with HAND in the context of aging. Here, we report FGF overexpression curtails gp120-induced neurotoxicity in a double transgenic mouse model. Furthermore, our data show disparities in brain neurotrophic factor levels may be exacerbated in HIV patients over 50 years of age. In this review, we discuss the most recent findings on neurotrophins and HAND in the context of developing new therapies to combat HIV infection in the aging population.
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影响因子：
3.3
作者：
Boven, LA;Middel, J;Nottet, HSLM
通讯作者：
Nottet, HSLM
影响因子：
5.8
作者：
Corasaniti, MT;Bagetta, G;Nisticò, G
通讯作者：
Nisticò, G
影响因子：
3.8
作者：
Bagasra, O;Lavi, E;Pomerantz, RJ
通讯作者：
Pomerantz, RJ
DOI：
10.1523/jneurosci.0865-12.2012
发表时间：
2012-07-11
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Bachis A;Avdoshina V;Zecca L;Parsadanian M;Mocchetti I
通讯作者：
Mocchetti I
HIV-1 的细胞储存库及其在病毒持久性中的作用。
影响因子：
1
作者：
Alexaki A;Liu Y;Wigdahl B
通讯作者：
Wigdahl B