The enhancement of amyloid precursor protein and β-site amyloid cleavage enzyme 1 interaction: Amyloid-β production with aging

Zou, Lin; Yang, Rongxi; Zhang, Penghui; Dai, Yi

doi:10.3892/ijmm_00000358

Cited by 12 publications

(10 citation statements)

References 25 publications

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“…Amyloid precursor protein and beta-site amyloid cleavage protein (BACE-1) show increasing interactions within endosomes with ageing. A dominant negative RAB-5 inhibits this interaction and decreases Abeta production [55]. The disorganization of the endosomal membrane system may advance these age-associated diseases.…”

Section: Discussionmentioning

confidence: 99%

Rabx-5 Regulates RAB-5 Early Endosomal Compartments and Synaptic Vesicles in C. elegans

Sann

Crane

et al. 2012

PLoS ONE

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Early endosomal membrane compartments are required for the formation and recycling of synaptic vesicles, but how these compartments are regulated is incompletely understood. We performed a forward genetic screen in C. elegans for mutations that affect RAB-5 labeled early endosomal compartments in GABAergic motoneurons. Here we report the isolation and characterization of one mutation, rabx-5. The rabx-5 mutation leads to decreased intensity of YFP::RAB-5 in the cell soma but increased intensity in the synaptic and intersynaptic regions of the axon. This effect is due to the bias of the cycling state of RAB-5, and results from a change in the organization of the early endosomal compartment as well as the membrane binding state of RAB-5. Synaptic vesicle accumulation is altered in rabx-5 mutants, and synaptic transmission from cholinergic neurons is decreased. Early endosomal membrane compartments show disorganization with ageing and rabx-5 mutant animals age faster. These results suggest that rabx-5 regulation of RAB-5 compartments is important for maintaining proper synaptic function throughout the lifetime.

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Section: Discussionmentioning

confidence: 99%

Rabx-5 Regulates RAB-5 Early Endosomal Compartments and Synaptic Vesicles in C. elegans

Sann

Crane

et al. 2012

PLoS ONE

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“…Morphological and functional changes in the aged brain cause different types and degrees of neuropathological changes and neurobiological alterations ( 1 – 4 ). Aging of the brain leads to various changes, including oxidative stress, protein repair ability, DNA damage, autophagic degradation and neuronal activity in the aged brain ( 5 – 10 ).…”

Section: Introductionmentioning

confidence: 99%

Age-dependent changes in the protein expression levels of Redd1 and mTOR in the gerbil hippocampus during normal aging

Choi

Ahn

Park

et al. 2016

Molecular Medicine Reports

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Redd1, also known as RTP801/Dig2/DDIT4, is a stress-induced protein and a negative regulator of mammalian target of rapamycin (mTOR). Redd1 is also closely associated with oxidative stress and DNA damage. In the present study, age-related changes in the protein expression levels of mTOR and Redd1 were investigated using immunohistochemistry and western blot in the gerbil hippocampus at postnatal month (PM) 3, 6, 12 and 24. No significant differences were identified in the levels of mTOR among the experimental groups, whereas, the levels of phosphorylated mTOR decreased with age. The protein expression levels of Redd1 were observed to gradually increase with age; in the PM 24 group, the level was significantly increased (~189.2%), compared with the PM 3 group. In addition, Redd1 immunoreactivity was significantly increased in the hippocampal principal neurons of the PM 24 group, including the pyramidal cells in the hippocampus proper and granule cells in the dentate gyrus, compared with the other experimental groups. These results demonstrated that the protein expression of Redd1 in the hippocampus was markedly increased during normal aging, indicating that the age-related increase in the expression of Redd1 may be closely associated with age-related hippocampal change.

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“…7 The selfaggregating properties of Ab alone are insufficient to explain the accumulation of the peptide only in specific brain regions because healthy people normally produce soluble Ab in their brains, and, more importantly, Ab is a soluble component of all biological fluids. 8 Furthermore, in the sporadic form of the pathology, Ab deposition, as well as the development of AD, is an age-dependent phenomenon, while it is not completely established if Ab production increases with age [9][10][11] and if the longer Ab peptides such as Ab1-42 are central for the seeding of amyloid in the brain. 12 Therefore, another important aspect that has to be considered in AD is that metal ions such as copper and zinc accumulate within the plaque deposits and reach concentrations of 400 mM and 1 mM, respectively.…”

Section: Metallomicsmentioning

confidence: 99%

Metallostasis and amyloid β-degrading enzymes

2012

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Amyloid-Beta (Aβ) is a major constituent of senile plaques and one of the principle hallmarks of Alzheimer's disease (AD). The peptide is produced by proteolytic cleavage of the larger amyloid precursor protein (APP). Increased production and aggregation of the peptide are associated with pathology. Emerging evidence suggests that the steady-state levels of Aβ are determined by the balance between its production and degradation. For this reason, the tuning of the activity of enzymes that degrade Aβ may be a promising approach in the development of novel therapeutics aimed at reducing Aβ concentration by enhancing its removal. A great part of Aβ degrading enzymes are known to be metalloproteases. In the last decade increasing evidence supported the idea that metal ion homeostasis is affected in several regions of AD brain and metals play an important role in tuning enzyme activity. There are three main different pathways by which metal ions can affect the proteolytic enzymes responsible for Aβ peptides degradation, as metal ions can: (i) form complexes with Aβ peptides that are not easily degraded; (ii) directly bind to degradative enzymes; (iii) produce signalling cascades that alter enzymes activity involved in Aβ catabolism. In the current literature the three points mentioned above are very often puzzled, resulting in a quite fragmentary scenario. The aim of this work is to find a link between metal ion homeostasis and Aβ degradation by separating and analysing the three different pathways proposed.

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The enhancement of amyloid precursor protein and β-site amyloid cleavage enzyme 1 interaction: Amyloid-β production with aging

Cited by 12 publications

References 25 publications

Rabx-5 Regulates RAB-5 Early Endosomal Compartments and Synaptic Vesicles in C. elegans

Rabx-5 Regulates RAB-5 Early Endosomal Compartments and Synaptic Vesicles in C. elegans

Age-dependent changes in the protein expression levels of Redd1 and mTOR in the gerbil hippocampus during normal aging

Metallostasis and amyloid β-degrading enzymes

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