Regulation of APP cleavage by α‐, β‐ and γ‐secretases

Nunan, Janelle; Small, David H.

doi:10.1016/s0014-5793(00)02076-7

Cited by 454 publications

(328 citation statements)

References 51 publications

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“…For example, the leakage of overproduced intra-axonal Aβ or extra-axonal proteolysis of the leaked amyloid precursor protein may result in Aβ plaques [33] , which may explain the Aβ plaques observed in brain areas with unimpaired neural functions [2,11] . Axonal leakage may be present at axon terminals of affected neurons located far from their termination areas, however, these areas may still exhibit unimpaired function if their neurons are not affected despite the presence of plaques.…”

Section: Discussionmentioning

confidence: 99%

The origin and development of plaques and phosphorylated tau are associated with axonopathy in Alzheimer’s disease

Xiao

Wang

et al. 2011

Neurosci. Bull.

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Objective The production of neurotoxic β-amyloid and the formation of hyperphosphorylated tau are thought to be critical steps contributing to the neuropathological mechanisms in Alzheimer's disease (AD). However, there remains an argument as to their importance in the onset of AD. Recent studies have shown that axonopathy is considered as an early stage of AD. However, the exact relationship between axonopathy and the origin and development of classic neuropathological changes such as senile plaques (SPs) and neurofi brillary tangles (NFTs) is unclear. The present study aimed to investigate this relationship. Methods Postmortem tracing, combined with the immunohistochemical or immunofl uorescence staining, was used to detect axonopathy and the formation of SPs and NFTs. Results "Axonal leakage"-a novel type of axonopathy, was usually accompanied with the extensive swollen axons and varicosities, and was associated with the origin and development of Aβ plaques and hyperphosphorylated tau in the brains of AD patients. Conclusion Axonopathy, particularly axonal leakage, might be a key event in the initiation of the neuropathological processes in AD.

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Section: Discussionmentioning

confidence: 99%

The origin and development of plaques and phosphorylated tau are associated with axonopathy in Alzheimer’s disease

Xiao

Wang

et al. 2011

Neurosci. Bull.

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“…for 15 days) accompanied by AChE activity restoration and cognitive improvement in the Morris Water Maze test has been observed in the STZ-icv treated mice (Sharma et al 2008). This effect has been associated with the findings that HIV protease has structural homology to beta-secretase 1 (BACE) (Hong et al 2000) and thus can modulate BACE activity, and consequently, possibly, the amount of amyloid-β formation (Nunan and Small 2000). Although a quite a number of trials has been conducted with Ginkgo biloba in demented patients, a…”

Section: Nosmentioning

confidence: 99%

What have we learned from the streptozotocin-induced animal model of sporadic Alzheimer’s disease, about the therapeutic strategies in Alzheimer’s research

et al. 2012

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“…The amyloidogenic pathway leading to Aβ production occurs by sequential cleavage of APP by β-secretase and subsequently by γ-secretase [43,56]. β-secretase has now been identified as beta-site APP cleaving enzyme or BACE [65].…”

Section: Introductionmentioning

confidence: 99%

Alpha- and beta-secretase activity as a function of age and beta-amyloid in Down syndrome and normal brain

Nistor

Don

Parekh

et al. 2007

Neurobiology of Aging

110

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Aged individuals with Down syndrome (DS) develop Alzheimer's disease (AD) neuropathology by the age of 40 years. The purpose of the current study was to measure age-associated changes in APP processing in 36 individuals with DS (5 months-69 years) and in 26 controls (5 months-100 years). Alpha-secretase significantly decreased with age in DS, particularly in cases over the age of 40 years and was stable in controls. The levels of C-terminal fragments of APP reflecting alphasecretase processing (CTF-alpha) decreased with age in both groups. In both groups, there was significant increase in beta-secretase activity with age. CTF-beta remained constant with age in controls suggesting compensatory increases in turnover/clearance mechanisms. In DS, young individuals had the lowest CTF-beta levels that may reflect rapid conversion of beta-amyloid (Aβ) to soluble pools or efficient CTF-beta clearance mechanisms. Treatments to slow or prevent AD in the general population targeting secretase activity may be more efficacious in adults with DS if combined with approaches that enhance Aβ degradation and clearance.

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Regulation of APP cleavage by α‐, β‐ and γ‐secretases

Cited by 454 publications

References 51 publications

The origin and development of plaques and phosphorylated tau are associated with axonopathy in Alzheimer’s disease

The origin and development of plaques and phosphorylated tau are associated with axonopathy in Alzheimer’s disease

What have we learned from the streptozotocin-induced animal model of sporadic Alzheimer’s disease, about the therapeutic strategies in Alzheimer’s research

Alpha- and beta-secretase activity as a function of age and beta-amyloid in Down syndrome and normal brain

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