Bridging the gap: large animal models in neurodegenerative research.
Bridging the gap: large animal models in neurodegenerative research.
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弥合差距：神经退行性研究中的大动物模型。
DOI：
10.1007/s00335-017-9687-6
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发表时间：
2017-08
期刊：
影响因子：
--
通讯作者：
Wishart TM
中科院分区：
文献类型：
--
作者：
Eaton SL;Wishart TM
世界卫生组织宣布神经系统疾病是当今世界最大的公共卫生风险之一。然而，尽管这种关切日益增加，但对其中许多情况的基本机制仍然知之甚少。这可能部分是由于起始损伤的表面多样性，从遗传（如共济失调和溶酶体储存障碍）到蛋白质错误折叠和聚集（即朊病毒），以及主要未知病因（即阿尔茨海默病和帕金森病）。然而，由于人类神经系统的复杂性、明显的选择性区域脆弱性和差异性退行性进展，阐明机械调节的努力也可能受到阻碍。阐明这些病因的关键是确定从疾病进展的早期到晚期发生的区域分子级联。虽然许多分子数据已经在人类疾病的末期从尸检分析中捕获，但疾病的非常早期阶段通常是明显无症状的，即使它们不是，从“受影响”的患者和“对照”的多个大脑区域重复采样既不道德也不可能。因此，模型系统成为阐明这些复杂的神经退行性疾病的机制的基础。然而，找到一个精确模仿人类状况的模型可能具有挑战性和昂贵。虽然细胞和无脊椎动物模型经常用于神经退行性研究，并且无疑产生了许多有用的数据，但这些系统相对简单的性质使得从这种独立模型中获得的见解在翻译时受到限制。鉴于基因编辑技术的最新进展，在高阶物种中生成新模型的选择为该领域开辟了新的和令人兴奋的可能性。因此，在这篇综述中，我们解释了一些原因，为什么更大的动物模型往往出现给人类神经系统疾病的一个更强大的重演，为什么他们可能是一个关键的垫脚石有效的治疗翻译。
The world health organisation has declared neurological disorders as one of the greatest public health risks in the world today. Yet, despite this growing concern, the mechanisms underpinning many of these conditions are still poorly understood. This may in part be due to the seemingly diverse nature of the initiating insults ranging from genetic (such as the Ataxia’s and Lysosomal storage disorders) through to protein misfolding and aggregation (i.e. Prions), and those of a predominantly unknown aetiology (i.e. Alzheimer’s and Parkinson’s disease). However, efforts to elucidate mechanistic regulation are also likely to be hampered because of the complexity of the human nervous system, the apparent selective regional vulnerability and differential degenerative progression. The key to elucidating these aetiologies is determining the regional molecular cascades, which are occurring from the early through to terminal stages of disease progression. Whilst much molecular data have been captured at the end stage of disease from post-mortem analysis in humans, the very early stages of disease are often conspicuously asymptomatic, and even if they were not, repeated sampling from multiple brain regions of “affected” patients and “controls” is neither ethical nor possible. Model systems therefore become fundamental for elucidating the mechanisms governing these complex neurodegenerative conditions. However, finding a model that precisely mimics the human condition can be challenging and expensive. Whilst cellular and invertebrate models are frequently used in neurodegenerative research and have undoubtedly yielded much useful data, the comparatively simplistic nature of these systems makes insights gained from such a stand alone model limited when it comes to translation. Given the recent advances in gene editing technology, the options for novel model generation in higher order species have opened up new and exciting possibilities for the field. In this review, we therefore explain some of the reasons why larger animal models often appear to give a more robust recapitulation of human neurological disorders and why they may be a critical stepping stone for effective therapeutic translation.
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用于研究亨廷顿病发病机制和治疗的转基因动物模型。
DOI：
10.2147/dddt.s58470
发表时间：
2015
期刊：
Drug design, development and therapy
影响因子：
--
作者：
Chang R;Liu X;Li S;Li XJ
通讯作者：
Li XJ
影响因子：
3.1
作者：
Heuer E;Rosen RF;Cintron A;Walker LC
通讯作者：
Walker LC
影响因子：
11.2
作者：
Duque, Sandra I.;Arnold, W. David;Odermatt, Philipp;Li, Xiaohui;Porensky, Paul N.;Schmelzer, Leah;Meyer, Kathrin;Kolb, Stephen J.;Schuemperli, Daniel;Kaspar, Brian K.;Burghes, Arthur H. M.
通讯作者：
Burghes, Arthur H. M.
DOI：
10.1073/pnas.1504955112
发表时间：
2015-09-08
影响因子：
11.1
作者：
Bowen, Anthony;Casadevall, Arturo
通讯作者：
Casadevall, Arturo
影响因子：
4.3
作者：
Hall VJ;Lindblad MM;Jakobsen JE;Gunnarsson A;Schmidt M;Rasmussen MA;Volke D;Zuchner T;Hyttel P
通讯作者：
Hyttel P