Unraveling the mystery: How autophagy deficiency in dopaminergic neurons drives human Parkinson's disease.

IF 2.9 3区 医学 Q2 NEUROSCIENCES
Sachiko Noda, Nobutaka Hattori
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引用次数: 0

Abstract

Alpha-synuclein (α-synuclein), a key component of Lewy body pathology, is a classical hallmark of Parkinson's disease. In previous studies, our group has examined dopaminergic neuron-specific Atg7 autophagy-deficient mice, observing α-synuclein aggregation in vivo. This pathological process led to dopamine neuron loss and age-related motor impairments. Further, in a recent study, we developed a new mouse model by crossing human α-synuclein bacterial artificial chromosome transgenic mice with dopaminergic neuron-specific Atg7 conditional knockout mice to further investigate these mechanisms. These model mice exhibited accelerated Lewy body-like pathology and motor dysfunction, providing additional evidence that autophagy deficiency exacerbates synuclein toxicity in vivo. This nano-review provides essential clues that autophagy deficiency in dopamine neurons may contribute to the onset of human synuclein diseases.

解开谜团:多巴胺能神经元的自噬缺陷如何驱动人类帕金森病。
α-突触核蛋白(α-synuclein)是路易体病理的重要组成部分,是帕金森病的典型标志。在之前的研究中,本课组对多巴胺能神经元特异性Atg7自噬缺陷小鼠进行了研究,在体内观察到α-突触核蛋白聚集。这一病理过程导致多巴胺神经元丢失和与年龄相关的运动障碍。此外,在最近的研究中,我们建立了一种新的小鼠模型,将人α-突触核蛋白细菌人工染色体转基因小鼠与多巴胺能神经元特异性Atg7条件敲除小鼠杂交,以进一步研究这些机制。这些模型小鼠表现出加速的路易体样病理和运动功能障碍,提供了自噬缺陷加剧体内突触核蛋白毒性的额外证据。这项纳米综述为多巴胺神经元自噬缺陷可能导致人类突触核蛋白疾病的发生提供了重要线索。
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来源期刊
Molecular Brain
Molecular Brain NEUROSCIENCES-
CiteScore
7.30
自引率
0.00%
发文量
97
审稿时长
>12 weeks
期刊介绍: Molecular Brain is an open access, peer-reviewed journal that considers manuscripts on all aspects of studies on the nervous system at the molecular, cellular, and systems level providing a forum for scientists to communicate their findings. Molecular brain research is a rapidly expanding research field in which integrative approaches at the genetic, molecular, cellular and synaptic levels yield key information about the physiological and pathological brain. These studies involve the use of a wide range of modern techniques in molecular biology, genomics, proteomics, imaging and electrophysiology.
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