Alzheimer’s disease(AD)is the most common age-dependent disease of dementia,and there is currently no cure available.This hallmark pathologies of AD are the presence of amyloid plaques and neurofibrillary tangles.Alt...Alzheimer’s disease(AD)is the most common age-dependent disease of dementia,and there is currently no cure available.This hallmark pathologies of AD are the presence of amyloid plaques and neurofibrillary tangles.Although the exact etiology of AD remains a mystery,studies over the past 30 have shown that abnormal generation or accumulation of β-amyloid peptides(Aβ)is likely to be a predominant early event in AD pathological development.Aβ is generated from amyloid precursor protein(APP)via proteolytic cleavage by β-site APP cleaving enzyme 1(BACE1).Chemical inhibition of BACE1 has been shown to reduce Aβ in animal studies and in human trials.While BACE1 inhibitors are currently being tested in clinical trials to treat AD patients,it is highly important to understand whether BACE1 inhibition will significantly impact cognitive functions in AD patients.This review summarizes the recent studies on BACE1 synaptic functions.This knowledge will help to guide the proper use of BACE1 inhibitors in AD therapy.展开更多
基金R Yan is supported by grants(MH103942,NS074256 and AG046929)from the National Institutes of Health.
文摘Alzheimer’s disease(AD)is the most common age-dependent disease of dementia,and there is currently no cure available.This hallmark pathologies of AD are the presence of amyloid plaques and neurofibrillary tangles.Although the exact etiology of AD remains a mystery,studies over the past 30 have shown that abnormal generation or accumulation of β-amyloid peptides(Aβ)is likely to be a predominant early event in AD pathological development.Aβ is generated from amyloid precursor protein(APP)via proteolytic cleavage by β-site APP cleaving enzyme 1(BACE1).Chemical inhibition of BACE1 has been shown to reduce Aβ in animal studies and in human trials.While BACE1 inhibitors are currently being tested in clinical trials to treat AD patients,it is highly important to understand whether BACE1 inhibition will significantly impact cognitive functions in AD patients.This review summarizes the recent studies on BACE1 synaptic functions.This knowledge will help to guide the proper use of BACE1 inhibitors in AD therapy.
