| 摘要 |
<p>A novel Asp-ase activity, referred to as BACE secretase/sheddase, has been found to cleave the ectoddomain of BACE after Asp379 (SQDD↓) and Asp407 (VVFD↓), and likely after Asp451 (PQTD↓). The cleavage of BACE by BACE secretase/sheddase renders BACE soluble which in turns appears to enhance the generation of the amyloidogenic peptide Aβ, which has been implicated as a major factor in the etiology of Alzheimer's Disease. The current invention concerns the modulation of this novel BACE secretase/sheddase activity for such applications as the prevention or treatment of a neurodegenerative disorder that is characterized by the generation of Aβ protein, including Alzheimer's Disease. The invention further comprises a method for the identification of an agent that can alter the ability of BACE secretase/sheddase to associate with and process a known substrate, a method of determining whether an individual is at risk of developing a neurodegenerative disorder that is characterized by the generation of Aβ protein (such as Alzheimer's Disease) and a kit comprising a vessel or vessels containing BACE secretase/sheddase as well as at least one known substrate of this enzyme, namely, BACE or BACE fragments, or the indirect substrate βAPP.</p> |
