Metals and Alzheimer's disease.
Metals and Alzheimer's disease.
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DOI：
10.3233/jad-2006-102-303
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发表时间：
2006
期刊：
影响因子：
--
通讯作者：
P. Adlard;A. Bush
中科院分区：
文献类型：
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作者：
P. Adlard;A. Bush
越来越多的证据支持淀粉样β蛋白前体（AbetaPP）及其蛋白水解片段β淀粉样蛋白（Abeta）在金属离子稳态中的作用。此外，锌和铜等金属离子可以与 AbetaPP 和 Abeta 相互作用，通过参与这些正常细胞蛋白的聚集和活性氧的生成，从而加剧阿尔茨海默病。此外，金属离子可能与其他几种 AD 相关途径相互作用，包括参与神经原纤维缠结形成、AbetaPP 分泌酶裂解和 Abeta 蛋白水解降解的途径。因此，金属离子稳态的失调（如衰老和 AD 中所发生的那样）可能会形成一种环境，从而促成和加速 AD 等退行性疾病。这为新型治疗干预措施提供了广泛的生化前沿。
There is increasing evidence to support a role for both the amyloid beta-protein precursor (AbetaPP) and its proteolytic fragment, amyloid beta (Abeta), in metal ion homeostasis. Furthermore, metal ions such as zinc and copper can interact with both AbetaPP and Abeta to potentiate Alzheimer's disease by participating in the aggregation of these normal cellular proteins and in the generation of reactive oxygen species. In addition, metal ions may interact on several other AD-related pathways, including those involved in neurofibrillary tangle formation, secretase cleavage of AbetaPP and proteolytic degradation of Abeta. As such, a dysregulation of metal ion homeostasis, as occurs with both aging and in AD, may foster an environment that can both precipitate and accelerate degenerative conditions such as AD. This offers a broad biochemical front for novel therapeutic interventions.