Beyond Krabbe's disease: The potential contribution of galactosylceramidase deficiency to neuronal vulnerability in late-onset synucleinopathies.
Beyond Krabbe's disease: The potential contribution of galactosylceramidase deficiency to neuronal vulnerability in late-onset synucleinopathies.
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DOI：
10.1002/jnr.23751
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发表时间：
2016-11
影响因子：
4.2
通讯作者：
Bongarzone, Ernesto R.
中科院分区：
文献类型：
--
作者：
Marshall, Michael S.;Bongarzone, Ernesto R.
关键词：
近年来，对迟发性神经退行性疾病背后的病理生理机制的新见解来自意想不到的来源。具体而言，已发现最常影响婴儿的称为溶酶体贮积病的遗传性代谢疾病组与成人神经退行性疾病具有惊人的相似性。最值得注意的是高雪氏病被鉴定为帕金森氏病的合并症。最近在另一种溶酶体贮积病Krabbe病中发现了α-突触核蛋白的神经元聚集体，我们提出了在成人突触核蛋白病和Krabbe病之间存在类似联系的想法。这两种疾病之间的相似性，包括Twitch小鼠（Krabbe病的真实小鼠模型）脑中α-突触核蛋白聚集的模式，脂质膜动力学的变化以及突触功能和巨自噬的可能功能障碍，强调了Krabbe病和迟发性突触核蛋白病之间的联系。沉默的GALC突变甚至可能构成某些患者发生帕金森病的风险因素。需要更多的研究来明确确定任何联系和这一假设的有效性，但这种联系将证明是非常宝贵的，可以根据我们目前对Krabbe病的理解开发帕金森病的新治疗靶点，并建立新的生物标志物来识别高危患者。
New insights into the pathophysiological mechanisms behind late onset neurodegenerative diseases have come from unexpected sources in recent years. Specifically, the group of inherited metabolic disorders known as lysosomal storage diseases that most commonly affect infants has been found to have surprising similarities with adult neurodegenerative disorders. Most notable has been the identification of Gaucher’s disease as a co-morbidity for Parkinson’s disease. Prompted by the recent identification of neuronal aggregates of α-synuclein within another lysosomal storage disease, Krabbe’s disease, we propose the idea that a similar connection exists between adult synucleionopathies and Krabbe. Similarities between the two diseases, including the pattern of α-synuclein aggregation in the brain of the Twitcher mouse (the authentic murine model of Krabbe’s disease), changes to lipid membrane dynamics, and possible dysfunction in synaptic function and macroautophagy underline a link between Krabbe’s disease and late onset synucleinopathies. Silent GALC mutations may even constitute a risk factor for the development of Parkinson’s in certain patients. More research is required to definitively identify any link and the validity of this hypothesis, but such connection would prove invaluable for developing novel therapeutic targets for Parkinson’s based on our current understanding of Krabbe’s disease and establishing new biomarkers for the identification of at-risk patients.
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影响因子：
3.8
作者：
Ribbens, Jameson. J.;Moser, Ann B.;Maegawa, Gustavo H. B.
通讯作者：
Maegawa, Gustavo H. B.
影响因子：
5.3
作者：
White, Adam B.;Givogri, Maria I.;Bongarzone, Ernesto R.
通讯作者：
Bongarzone, Ernesto R.
影响因子：
2.9
作者：
Martinez, Zak;Zhu, Min;Fink, Anthony L.
通讯作者：
Fink, Anthony L.
影响因子：
64.5
作者：
Mazzulli JR;Xu YH;Sun Y;Knight AL;McLean PJ;Caldwell GA;Sidransky E;Grabowski GA;Krainc D
通讯作者：
Krainc D
DOI：
10.1186/alzrt109
发表时间：
2012
期刊：
Alzheimer's research & therapy
影响因子：
--
作者：
Marsh SE;Blurton-Jones M
通讯作者：
Blurton-Jones M