Acumen Pharmaceuticals, Glenview, IL 60025, USA.
Neuropharmacology. 2010 Sep-Oct;59(4-5):230-42. doi: 10.1016/j.neuropharm.2010.07.012. Epub 2010 Jul 23.
Today, it is widely accepted that ADDLs, soluble oligomeric assemblies of the amyloid beta peptide, play a prominent role in triggering the cognitive deficits and neurodegeneration that constitute Alzheimer's disease (AD). Within the past decade, the longstanding emphasis on fibrillar deposits and neuronal death has given way to a new paradigm involving ADDL-triggered aberrant synaptic signaling and consequent memory malfunction and neurodegeneration. As with any paradigm shift in biology, not all molecular details have been elucidated, and not all AD scientists are fully subscribed. Nevertheless, the ADDL paradigm affords a promising framework for ongoing AD research and for development of the first therapeutics endowed with the dual capabilities of immediate symptom reversal and long-term disease modification. In this review we provide a brief account of the discovery of ADDLs, followed by a summary of key results that address questions concerning ADDL structure and assembly, biological activity and therapeutic possibilities.
如今，人们普遍认为淀粉样肽的可溶性寡聚体（ADDLs）在引发阿尔茨海默病（AD）的认知缺陷和神经退行性变方面起着重要作用。在过去的十年中，对纤维状沉积物和神经元死亡的长期关注已经让位于一个新的范式，该范式涉及 ADDL 引发的异常突触信号传递，以及随之而来的记忆功能障碍和神经退行性变。与生物学中的任何范式转变一样，并非所有分子细节都已阐明，并非所有 AD 科学家都完全认同。然而，ADDL 范式为正在进行的 AD 研究和开发具有立即缓解症状和长期疾病改善双重功能的第一种治疗方法提供了一个有希望的框架。在这篇综述中，我们简要介绍了 ADDLs 的发现，随后总结了关键结果，这些结果涉及 ADDL 的结构和组装、生物学活性和治疗可能性等问题。
