Xia Weiming
Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, 77 Ave Louis Pasteur, Boston, MA 02115, USA.
Curr Opin Investig Drugs. 2003 Jan;4(1):55-9.
Neuritic plaques composed of amyloid beta-protein (A beta) are an early and invariant neuropathological feature of Alzheimer's disease (AD). The current preclinical search for drugs is mainly focused on decreasing A beta production by inhibiting beta- or gamma-secretase, blocking the formation of these plaques by preventing A beta protofibril and fibril formation, and alleviating the toxic effects of neuritic plaque deposition. Increasing numbers of drugs currently used as therapies for other diseases are now entering clinical trials for AD, but the molecular targets of these drugs and their relevance to A beta toxicity needs to be thoroughly addressed. This knowledge will allow us to fully understand the A beta-related pathways in AD pathogenesis and explore novel therapeutic interventions.
由β-淀粉样蛋白(Aβ)组成的神经炎性斑块是阿尔茨海默病(AD)早期且恒定的神经病理学特征。目前临床前的药物研究主要集中在通过抑制β-或γ-分泌酶来减少Aβ的产生,通过防止Aβ原纤维和纤维的形成来阻止这些斑块的形成,以及减轻神经炎性斑块沉积的毒性作用。越来越多目前用于治疗其他疾病的药物正在进入AD的临床试验,但这些药物的分子靶点及其与Aβ毒性的相关性需要得到彻底解决。这些知识将使我们能够充分了解AD发病机制中与Aβ相关的途径,并探索新的治疗干预措施。