Tracking extranigral degeneration in animal models of Parkinson's disease: quest for effective therapeutic strategies.
Tracking extranigral degeneration in animal models of Parkinson's disease: quest for effective therapeutic strategies.
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DOI：
10.1111/j.1471-4159.2011.07320.x
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发表时间：
2011-08
影响因子：
4.7
通讯作者：
Banik NL
中科院分区：
文献类型：
--
作者：
Knaryan VH;Samantaray S;Le Gal C;Ray SK;Banik NL
散发性帕金森病（PD）现在被解释为一种复杂的神经系统疾病，其中投射神经元主要受损。这样的解释是基于路易体（LB）和路易神经突（LN）病理的映射。人类疾病的症状非常广泛，从临床前非运动症状和临床运动症状到晚期常见的认知差异。现有的对症治疗使明显的药物无反应症状进一步复杂化。通过同化黑质纹状体退行性机制的神经外退行性通路，PD得到了更好的理解。“神经节外”一词最早出现于上世纪90年代，通过消除过程更严格地定义了神经节病理。然而，随着临床医生逐渐发现PD症状对金标准药物左旋多巴无反应，PD症状的定义被重新定义。非运动症状前驱症状到运动症状，就像临床前到临床一样，并共同出现了PD的黑质变性和神经质外变性的概念。虽然黑质纹状体变性是锥体外运动特征的神经生物学基础，但神经外变性证实了绝大多数分散的中枢、外周和肠神经系统核的其他变化，这些变化共同解释了人类疾病的整体症状。作为神经节外部位，脊髓也与帕金森病的进展有关。脊髓神经元通过下行和上行通路与上中枢神经系统结构相连，参与运动和感觉回路，控制运动和反射。一些临床和体内研究已经证明了帕金森病相关的脊髓退行性过程的迹象，这导致最近考虑脊髓作为一个潜在的治疗应用领域。综上所述，本文旨在探讨现有的动物模型如何能够真实地反映人类疾病，以促进帕金森病的研究。本文简要地回顾了神经节外变性研究的发展，然后根据临床PD的最新发现对动物模型进行了调查。总之，它可能有助于制定有效的治疗策略。
Sporadic Parkinson’s disease (PD) is now interpreted as a complex nervous system disorder in which the projection neurons are predominantly damaged. Such an interpretation is based on mapping of Lewy body (LB) and Lewy neurite (LN) pathology. Symptoms of the human disease are much widespread, which span from preclinical nonmotor symptoms and clinical motor symptoms to cognitive discrepancies often seen in advanced stages. Existing symptomatic treatments further complicate with overt drug-irresponsive symptoms. PD is better understood by assimilation of extranigral degenerative pathways with nigrostriatal degenerative mechanisms. The term ‘extranigral’ appeared first in ‘90s’ to more rigorously define the nigral pathology by process of elimination. However, as clinicians progressively identified PD symptoms unresponsive to the gold standard drug L-DOPA, definitions of PD symptoms were redefined. Nonmotor symptoms prodromal to motor symptoms just as preclinical to clinical, and conjointly emerged the concept of nigral versus extranigral degeneration in PD. While nigrostriatal degeneration is responsible for the neurobiological substrates of extrapyramydal motor features, extranigral degeneration corroborates a vast majority of other changes in discrete central, peripheral, and enteric nervous system nuclei which together account for global symptoms of the human disease. As an extranigral site, spinal cord has also been implicated in PD progression. Interconnected to the upper central nervous system structures with descending and ascending pathways, spinal neurons participate in movement and sensory circuits, controlling movement and reflexes. Several clinical and in vivo studies have demonstrated signs of parkinsonism-related degenerative processes in spinal cord, which led to recent consideration of spinal cord as an area of potential therapeutic applications. In nutshell, the review explores how the existing animal models can actually reflect the human disease in order to facilitate PD research. Evolution of extranigral degeneration studies has been succinctly revisited, followed by a survey on animal models in light of recent findings in clinical PD. Together, it may help to develop effective therapeutic strategies.
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影响因子：
3.7
作者：
Fournier M;Vitte J;Garrigue J;Langui D;Dullin JP;Saurini F;Hanoun N;Perez-Diaz F;Cornilleau F;Joubert C;Ardila-Osorio H;Traver S;Duchateau R;Goujet-Zalc C;Paleologou K;Lashuel HA;Haass C;Duyckaerts C;Cohen-Salmon C;Kahle PJ;Hamon M;Brice A;Corti O
通讯作者：
Corti O
影响因子：
4.2
作者：
Freichel, Christian;Neumann, Manuela;Kahle, Philipp J.
通讯作者：
Kahle, Philipp J.
影响因子：
2.5
作者：
Choi, Yeong-Gon;Park, Jae-Hyun;Lim, Sabina
通讯作者：
Lim, Sabina
影响因子：
2.9
作者：
Chera, H;Schaecher, KE;Banik, NL
通讯作者：
Banik, NL
DOI：
10.1126/science.1164901
发表时间：
2009-03-20
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Fuentes R;Petersson P;Siesser WB;Caron MG;Nicolelis MA
通讯作者：
Nicolelis MA