ABSTRACT

Mucopolysaccharidoses (MPS) are inherited metabolic diseases with strong neurological involvement. MPSs are caused by defects in lysosomal enzymes involved in the degradation of glycosaminoglycans (GAGs), which consequently accumulate into the lysosomes as primary storage. Macroautophagy/autophagy impairment is well known to drive neurodegeneration in MPSs, however, mechanisms underlying such dysfunction are still poorly understood. Recently, by studying a mouse model for MPS-III (Sanfilippo syndrome) we have shown that the progressive aggregation of amyloid proteins in neuronal cell bodies occurs downstream of the GAG storage and, in turn, impairs the autophagy pathway by affecting lysosomal-dependent autophagosome clearance

摘要

粘多糖贮积症 (MPS) 是遗传性代谢疾病，具有强烈的神经系统受累。MPS 是由参与糖胺聚糖 (GAG) 降解的溶酶体酶的缺陷引起的，这些酶因此积累到溶酶体中作为主要储存。众所周知，巨自噬/自噬损伤会驱动 MPS 中的神经退行性变，然而，对这种功能障碍的潜在机制仍然知之甚少。最近，通过研究 MPS-III（Sanfilippo 综合征）的小鼠模型，我们发现神经元细胞体中淀粉样蛋白的进行性聚集发生在 GAG 储存的下游，进而通过影响溶酶体依赖性自噬体损害自噬途径清除