科研之友
微信
新浪微博
Facebook
分享链接
摘要
Amyloid-beta (A beta), A beta(40), A beta(42), and, recently, A beta(25-35) have been directly implicated in the pathogenesis of Alzheimer's disease. We have studied the effects of A beta on neuronal death, reactive oxygen species (ROS) production, and synaptic assembling in neurons in primary culture. A beta(25-35), A beta(40), and A beta(42) significantly decreased neuronal viability, although A beta(25-35) showed a higher effect. A beta(25-35) showed a more penetrating ability to reach mitochondria while A beta(40) did not enter the neuronal cytosol and A beta(42) was scarcely internalized. We did not observe a direct correlation between ROS production and cell death because both A beta(40) and A beta(42) decreased neuronal viability but A beta(40) did not change ROS production. Rather, ROS production seems to correlate with the penetrating ability of each A beta. No significant differences were found between A beta(40) and A beta(42) regarding the extent of the deleterious effects of both peptides on neuronal viability or synaptophysin expression. However, A beta(40) elicited a clear delocalization of PSD-95 and synaptotagmin from prospective synapsis to the neuronal soma, suggesting the occurrence of a crucial effect of A beta(40) on synaptic disassembling. The formation of A beta(40)-or A beta(42)-serum albumin complexes avoided the effects of these peptides on neuronal viability, synaptophysin expression, and PSD-95/synaptotagmin disarrangement suggesting that sequestration of A beta by albumin prevents deleterious effects of these peptides. We can conclude that A beta borne by albumin can be safely transported through body fluids, a fact that may be compulsory for A beta disposal by peripheral tissues.
- 出版日期2017
