Functional Roles of Amyloid-β Protein Precursor and Amyloid-β Peptides: Evidence from Experimental Studies

摘要: Abstract Amyloid-beta (Abeta) has remained a central feature in research into Alzheimer's disease (AD). Yet the function of amyloid-beta protein precursor (AbetaPP) and its processing products nervous system is controversial. This review examines experimental literature from cell cultures to transgenic AD brain injury models with special emphasis on functional role AbetaPP AbetaPP-derived peptides. knock-out mice exhibit severe metabolic abnormalities behavioral deficits, indicating an important physiological AbetaPP. Also, increasing body evidence suggests that while Abeta undoubtedly linked neurodegeneration, soluble amino-terminal fragment (sAbetaPPalpha) neuroprotective, neurotrophic, adhesive functions. Moderate overexpression human rodents does not produce apparent pathology no significant effect cognitive or sensorimotor behavior and, surprisingly, may even provide histological neuroprotection against focal cerebral ischemia. In contrast, phenotypes more show impaired performance, increased vulnerability ischemia trauma, less favorable outcome before deposition. A delicate balance seems determine consequences. Thus, it tempting speculate promotion alpha-secretase-mediated cleavage AbetaPP, which leads sAbetaPPalpha production, provides novel therapeutic strategy treatment injury.