The Lysosomal System in Neuronal Cell Death: A Review a
The Lysosomal System in Neuronal Cell Death: A Review a
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神经细胞死亡中的溶酶体系统：综述
DOI：
--
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发表时间：
1993
影响因子：
5.2
通讯作者：
A. Cataldo
中科院分区：
文献类型：
--
作者：
R. Nixon;A. Cataldo
溶酶体系统通常被认为是神经元受压或死亡的一个重要的形态标志。溶酶体或其组成的水解酶在不同的神经病理状态下被认为是细胞死亡的起始者和直接诱导者，细胞修复和再补偿的促进剂，细胞终末溶解的效应者，或细胞碎片的自溶清除剂。有限的数据和方法的限制往往不允许歧视这些潜在的作用。在所有形式的神经变性中，可以推测，在细胞解体的最后阶段，溶酶体最终破裂并释放各种促进细胞自溶的水解酶。除了这一可能是细胞死亡的普遍因素外，溶酶体系统在神经退化状态中的参与程度也有很大差异。在许多情况下，溶酶体系统激活的形态证据很少或检测不到。在其他情况下，只有当细胞损伤的其他形态迹象也存在时，溶酶体激活才明显。这种程度的参与可以被视为神经元试图补偿或修复损伤，或者是导致细胞溶解的晚期事件。溶酶体系统早期参与神经退行性变最常见的形式是异常储存轮廓或残留体(第三级溶酶体)在神经细胞内堆积。通常情况下，溶酶体受累可以追溯到溶酶体成分的原发缺陷或功能障碍，或者是加速或异常的膜破裂，导致溶酶体内修饰的抗消化底物的积聚。由于溶酶体系统的变化经常是惊人的，因此，溶酶体系统的变化是某些类型的代谢障碍的敏感形态指标；然而，对于大多数情况，它们是否反映了受损神经元的有益反应或促进细胞死亡和清除大脑碎片的机制仍有待确定。在致死性神经元损伤中，可能影响溶酶体反应的因素包括物种差异、神经元发育阶段、损伤持续时间和细胞死亡速度。在低等脊椎动物或无脊椎动物系统中，溶酶体系统可能比哺乳动物系统中与某些形式的神经细胞死亡更紧密地耦合在一起。
The lysosomal system has often been considered a prominent morphologic marker of distressed or dying neurons. Lysosomes or their constituent hydrolases have been viewed in different neuropathologic states as either initiators and direct agents of cell death, agents of cellular repair and recompensation, effectors of end-stage cellular dissolution, or autolytic scavengers of cellular debris. Limited data and limitations of methodology often do not allow these potential roles to be discriminated. In all forms of neurodegeneration, it may be presumed that lysosomes ultimately rupture and release various hydrolases that promote cell autolysis during the final stages of cellular disintegration. Beyond this perhaps universal contribution to cell death, the degree to which the lysosomal system may be involved in neurodegenerative states varies considerably. In many conditions, morphologic evidence for activation of the lysosomal system is minimal or undetectable. In other cases, lysosomal activation is evident only when other morphologic signs of cell injury are also present. This level of participation may be viewed as either an attempt by the neuron to compensate for or repair the injury or a late-stage event leading to cell dissolution. The early involvement of the lysosomal system in neurodegeneration occurs most commonly in the form of intraneuronal accumulations of abnormal storage profiles or residual bodies (tertiary lysosomes). Very often the lysosomal involvement can be traced to a primary defect or dysfunction of lysosomal components or to accelerated or abnormal membrane breakdown that leads to the buildup of modified digestion-resistant substrates within lysosomes. Because they are often striking, changes in the lysosomal system are a sensitive morphologic indicator of certain types of metabolic distress; however, whether they reflect a salutary response of a compromised neuron or a mechanism to promote cell death and removal of debris from the brain remains to be established for most conditions. Factors that may influence the lysosomal response during lethal neuronal injury include species differences, stage of neuronal development, duration of injury and pace of cell death. The lysosomal system may be more closely coupled to certain forms of neuronal cell death in lower vertebrate or invertebrate systems than in mammalian systems.
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影响因子：
56.9
作者：
IVY, GO;SCHOTTLER, F;LYNCH, G
通讯作者：
LYNCH, G
影响因子：
56.9
作者：
BROWN, MS;GOLDSTEIN, JL
通讯作者：
GOLDSTEIN, JL
DOI：
10.1073/pnas.89.5.1671
发表时间：
1992-03-01
影响因子：
11.1
作者：
NITSCH, RM;BLUSZTAJN, JK;WURTMAN, RJ
通讯作者：
WURTMAN, RJ
影响因子：
56.9
作者：
BROWN, MS;KOVANEN, PT;GOLDSTEIN, JL
通讯作者：
GOLDSTEIN, JL
赫曼斯基-普德拉克综合征中尿多萜醇排泄升高。
DOI：
10.1016/0002-9343(87)90446-3
发表时间：
1987
期刊：
The American journal of medicine
影响因子：
--
作者：
WitkopJr,CJ;Wolfe,LS;Cal,SX;White,JG;Townsend,D;Keenan,KM
通讯作者：
Keenan,KM