Loss of autophagy in dopaminergic neurons causes Lewy pathology and motor dysfunction in aged mice.
Loss of autophagy in dopaminergic neurons causes Lewy pathology and motor dysfunction in aged mice.
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DOI：
10.1038/s41598-018-21325-w
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发表时间：
2018-02-12
影响因子：
4.6
通讯作者：
Hattori N
中科院分区：
文献类型：
--
作者：
Sato S;Uchihara T;Fukuda T;Noda S;Kondo H;Saiki S;Komatsu M;Uchiyama Y;Tanaka K;Hattori N
结构性自噬的失活会导致神经元胞浆内包涵体的形成，但自噬受损与路易小体之间的关系以及体内形成的过程尚不清楚。突触核蛋白是LBS的一种成分，是帕金森病(PD)的典型特征。在这里，我们描述了多巴胺(DA)神经元特异性自噬缺陷小鼠的特征，并为LB的形成提供了体内证据。突触核蛋白沉积在p62之前，并导致含有突触核蛋白和p62的包裹体的形成。随着年龄的增长，突起中夹杂物的数量和大小逐渐增加，而胞体中的夹杂物数量和大小逐渐增加。这些包含可能会导致外围设备故障。结果：120周龄小鼠出现DA神经元丢失和包括后肢缺陷在内的运动功能障碍。来自自噬缺陷的p62聚集体可能充当“种子”，并可能是形成Lb的原因。
Inactivation of constitutive autophagy results in the formation of cytoplasmic inclusions in neurons, but the relationship between impaired autophagy and Lewy bodies (LBs) as well as the in vivo process of formation remains unknown. Synuclein, a component of LBs, is the defining characteristic of Parkinson’s disease (PD). Here, we characterize dopamine (DA) neuron–specific autophagy-deficient mice and provide in vivo evidence for LB formation. Synuclein deposition is preceded by p62 and resulted in the formation of inclusions containing synuclein and p62. The number and size of these inclusions were gradually increased in neurites rather than soma with aging. These inclusions may facilitate peripheral failures. As a result, DA neuron loss and motor dysfunction including the hindlimb defect were observed in 120-week-old mice. P62 aggregates derived from an autophagic defect might serve as “seeds” and can potentially be cause of LB formation.
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DOI：
10.1083/jcb.201003122
发表时间：
2010-09-20
期刊：
The Journal of cell biology
影响因子：
--
作者：
Winslow AR;Chen CW;Corrochano S;Acevedo-Arozena A;Gordon DE;Peden AA;Lichtenberg M;Menzies FM;Ravikumar B;Imarisio S;Brown S;O'Kane CJ;Rubinsztein DC
通讯作者：
Rubinsztein DC
影响因子：
6.4
作者：
Kanazawa, Toshiro;Uchihara, Toshiki;Mizusawa, Hidehiro
通讯作者：
Mizusawa, Hidehiro
影响因子：
13.3
作者：
Bartlett, Bryan J.;Isakson, Pauline;Finley, Kim D.
通讯作者：
Finley, Kim D.
影响因子：
5.3
作者：
Bedford, Lynn;Hay, David;Mayer, R. John
通讯作者：
Mayer, R. John
DOI：
10.1523/jneurosci.0209-12.2012
发表时间：
2012-11-14
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Ahmed I;Liang Y;Schools S;Dawson VL;Dawson TM;Savitt JM
通讯作者：
Savitt JM