Repression of Alzheimer's beta-Secretase

Liao, Francesca‐Fang; Wang, Ruishan; Park, Edwards A.

doi:10.18632/aging.100612

Cited by 1 publication

(1 citation statement)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…2,3 The conventional view of AD, according to the "amyloid hypothesis", is that β-amyloid (Aβ), the product of proteolytic cleavage of the large transmembrane Aβ precursor protein (AβPP), occupies a central place in the pathology of disease. 4,5 AD is characterized by increased load of Aβ in the brain, especially the peptides 42 amino acids in length, leading to accumulation of Aβ, amyloid plaques, neurofibrillary tangles, synaptic failure, neuronal cell death, excitotoxicity, inflammation, mitochondrial dysfunction, and oxidative stress. 3 In contrast, there is growing evidence that mitochondrial damage and oxidative stress lead to activation of the Aβ cascade.…”

Section: Introductionmentioning

confidence: 99%

Senescence-accelerated OXYS rats: A model of age-related cognitive decline with relevance to abnormalities in Alzheimer disease

et al. 2014

View full text Add to dashboard Cite

Senescence-accelerated OXYS rats are an experimental model of accelerated aging that was established from wistar stock via selection for susceptibility to cataractogenic effects of a galactose-rich diet and via subsequent inbreeding of highly susceptible rats. Currently, we have the 102nd generation of OXYS rats with spontaneously developing cataract and accelerated senescence syndrome, which means early development of a phenotype similar to human geriatric disorders, including accelerated brain aging. in recent years, our group found strong evidence that OXYS rats are a promising model for studies of the mechanisms of brain aging and neurodegenerative processes similar to those seen in Alzheimer disease (AD). The manifestation of behavioral alterations and learning and memory deficits develop since the fourth week of age, i.e., simultaneously with first signs of neurodegeneration detectable on magnetic resonance imaging and under a light microscope. in addition, impaired long-term potentiation has been demonstrated in OXYS rats by the age of 3 months. with age, neurodegenerative changes in the brain of OXYS rats become amplified. we have shown that this deterioration happens against the background of overproduction of amyloid precursor protein (AβPP), accumulation of β-amyloid (Aβ), and hyperphosphorylation of the tau protein in the hippocampus and cortex. The development of AMDlike retinopathy in OXYS rats is also accompanied by increased accumulation of Aβ in the retina. These published data suggest that the OXYS strain may serve as a spontaneous rat model of AD-like pathology and could help to decipher the pathogenesis of AD.

show abstract