Interaction Between Pp6068 Clone Protein And BACE1

Alzheimer's disease(AD) is a neurodegenerative disorder which is characterized clinically by progressive loss of memory and impairment of cognitive abilities. Neurofibrillary tangle(NFT) and senile plaque(SP) are the two histological characters found in the brain of AD patients.Recent researches have showed that the major component of SPs is Aβ(β-amyloid peptides).BACE1(β-site APP cleaving enzyme;APP,amyloid precursor protein),identified as a key enzyme during the Aβformation,has become one of the hotspots of Alzheimer's disease research.However, some pathophysiological functions of BACE1 and the underlying mechanisms still remain unclear.To further elucidate the role of BACE1 during the development of Alzheimer Disease,we utilized yeast two-hybrid system to identify BACE1-interacting proteins. Using the BACE1 carboxyl terminus(C_473-501) as the bait protein,we screened the human fetal brain cDNA library and acquired one novel protein:pp6068 clone protein.We constructed a pp6068 clone protein expression vector and expressed it in mammalian cells.Co-immunoprecipitantion in HEK 293T cells confirmed the interaction between pp6068 clone protein and BACE1.The overexpression of pp6068 clone protein in N2a/APP695 dramatically increases protein level of APP/βCTF and Aβ,both of which are hydrolysis products of BACE1.On the other hand,the increased expression of pp6068 clone protein decreaseα-secretase cleavage product of APP,sAPPα.Our data suggests that pp6068 clone protein may play a potential role in the regulation of BACE1 activity and affect the APP processing and Aβgeneration.Our research may contribute to further comprehension of proteins interacting with BACE1, and facilitate developments in Alzheimer's disease treatment.