¥ã-Secretase in Alzheimer¡¯s disease
ÇãÁö¿¬,
¼Ò¼Ó »ó¼¼Á¤º¸
ÇãÁö¿¬ ( Hur Ji-Yeun )
Memorial Sloan Kettering Cancer Center Chemical Biology Program
Abstract
Alzheimer¡¯s disease (AD) is caused by synaptic and neuronal loss in the brain. One of the characteristic hallmarks of AD is senile plaques containing amyloid ¥â-peptide (A¥â). A¥â is produced from amyloid precursor protein (APP) by sequential proteolytic cleavages by ¥â-secretase and ¥ã-secretase, and the polymerization of A¥â into amyloid plaques is thought to be a key pathogenic event in AD. Since ¥ã-secretase mediates the final cleavage that liberates A¥â, ¥ã-secretase has been widely studied as a potential drug target for the treatment of AD. ¥ã-Secretase is a transmembrane protein complex containing presenilin, nicastrin, Aph-1, and Pen-2, which are sufficient for ¥ã-secretase activity. ¥ã-Secretase cleaves >140 substrates, including APP and Notch. Previously, ¥ã-secretase inhibitors (GSIs) were shown to cause side effects in clinical trials due to the inhibition of Notch signaling. Therefore, more specific regulation or modulation of ¥ã-secretase is needed. In recent years, ¥ã-secretase modulators (GSMs) have been developed. To modulate ¥ã-secretase and to understand its complex biology, finding the binding sites of GSIs and GSMs on ¥ã-secretase as well as identifying transiently binding ¥ã-secretase modulatory proteins have been of great interest. In this review, decades of findings on ¥ã-secretase in AD are discussed.
Å°¿öµå
Alzheimer's disease
¿ø¹® ¹× ¸µÅ©¾Æ¿ô Á¤º¸
µîÀçÀú³Î Á¤º¸
SCI(E)
MEDLINE
KCI
KoreaMed
KAMS