Pompe disease: Shared and unshared features of lysosomal storage disorders.
Pompe disease: Shared and unshared features of lysosomal storage disorders.
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DOI：
10.1080/21675511.2015.1068978
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Raben N
中科院分区：
文献类型：
--
作者：
Lim JA;Kakhlon O;Li L;Myerowitz R;Raben N
庞贝病是一种遗传性溶酶体酸α-葡萄糖苷酶（GAA）缺乏症，是一种具有广泛临床表现的严重代谢性肌病。这是第一个公认的溶酶体储存疾病和第一个治疗（酶替代）已被批准的神经肌肉疾病。由于GAA是唯一在溶酶体酸性环境中将糖原水解为葡萄糖的酶，缺乏GAA会导致糖原在该细胞器内积累并随之增大。自该疗法引入以来，对该病的整体认识有了显著进展，但对肌肉损伤的病理生理仍未完全了解。病理级联的复杂图景涉及钙稳态紊乱、线粒体异常、功能失调的自噬、有毒不可降解物质的积累以及与衰老无关的脂褐素沉积的加速产生。本文讨论了庞贝病与其他溶酶体贮积性疾病的关系以及庞贝病的潜在治疗干预措施。
Pompe disease, an inherited deficiency of lysosomal acid α-glucosidase (GAA), is a severe metabolic myopathy with a wide range of clinical manifestations. It is the first recognized lysosomal storage disorder and the first neuromuscular disorder for which a therapy (enzyme replacement) has been approved. As GAA is the only enzyme that hydrolyses glycogen to glucose in the acidic environment of the lysosome, its deficiency leads to glycogen accumulation within and concomitant enlargement of this organelle. Since the introduction of the therapy, the overall understanding of the disease has progressed significantly, but the pathophysiology of muscle damage is still not fully understood. The emerging complex picture of the pathological cascade involves disturbance of calcium homeostasis, mitochondrial abnormalities, dysfunctional autophagy, accumulation of toxic undegradable materials, and accelerated production of lipofuscin deposits that are unrelated to aging. The relationship of Pompe disease to other lysosomal storage disorders and potential therapeutic interventions for Pompe disease are discussed.