Mutant Presenilin 2 Transgenic Mouse: Effect on an Age-Dependent Increase of Amyloid β-Protein 42 in the Brain

2002 ◽  
Vol 71 (1) ◽  
pp. 313-322 ◽  
Author(s):  
Fumitaka Oyama ◽  
Naoya Sawamura ◽  
Kimio Kobayashi ◽  
Maho Morishima-Kawashima ◽  
Takashi Kuramochi ◽  
...  
Keyword(s):  
Transgenic Mouse ◽  
Amyloid Β ◽  
Amyloid Β Protein ◽  
Β Protein ◽  
Age Dependent ◽  
Presenilin 2 ◽  
The Brain

Nobiletin, a flavone from Citrus depressa, induces gene expression and increases the protein level and activity of neprilysin in SK-N-SH cells

2014 ◽  
Vol 92 (5) ◽  
pp. 351-355 ◽  
Author(s):  
Hironori Fujiwara ◽  
Junko Kimura ◽  
Masahiro Sakamoto ◽  
Akihito Yokosuka ◽  
Yoshihiro Mimaki ◽  
...  
Keyword(s):  
Amyloid Β ◽  
Time Dependent ◽  
Amyloid Β Protein ◽  
Dependent Manner ◽  
Disease Modifying Drugs ◽  
Β Protein ◽  
Gene And Protein Expression ◽  
Polymerase Chain ◽  
Potential Strategy ◽  
The Brain

Neprilysin (NEP) is one of the candidate amyloid β protein (Aβ) degrading enzymes affecting brain Aβ clearance. This enzyme declines in the brain with age, which leads to the increased Aβ deposition in Alzheimer’s disease (AD). Pharmacological activation of NEP during the aging process, therefore, represents a potential strategy to prevent the development of AD. To examine the influence of nobiletin on neprilysin activity, we measured cellular NEP activity in SK-N-SH cells. Moreover, NEP expression was examined by using reverse transcription – polymerase chain reaction and Western blotting. Measurement of cellular NEP activity showed that nobiletin stimulated this in a dose- and time-dependent manner in SK-N-SH cells. Moreover, nobiletin increased the expression of NEP mRNA, and then the levels of NEP protein, also in a dose- and time-dependent manner. Our findings showed that nobiletin promoted NEP gene and protein expression, resulting in enhancement of cellular NEP activity in SK-N-SH cells. This compound could be a novel Aβ-degrading compound for use in the development of disease-modifying drugs to prevent and (or) cure AD.

scholarly journals Accumulation of Amyloid β-Protein in the Low-Density Membrane Domain Accurately Reflects the Extent of β-Amyloid Deposition in the Brain

2001 ◽  
Vol 158 (6) ◽  
pp. 2209-2218 ◽  
Author(s):  
Noriko Oshima ◽  
Maho Morishima-Kawashima ◽  
Haruyasu Yamaguchi ◽  
Masahiro Yoshimura ◽  
Shiro Sugihara ◽  
...  
Keyword(s):  
Amyloid Β ◽  
Amyloid Deposition ◽  
Low Density ◽  
Amyloid Β Protein ◽  
Membrane Domain ◽  
Β Protein ◽  
Β Amyloid ◽  
The Brain

scholarly journals Dietary cis-9, trans-11-conjugated linoleic acid reduces amyloid β-protein accumulation and upregulates anti-inflammatory cytokines in an Alzheimer’s disease mouse model

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yu Fujita ◽  
Kuniyuki Kano ◽  
Shigenobu Kishino ◽  
Toshihiro Nagao ◽  
Xuefeng Shen ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Linoleic Acid ◽  
Mouse Model ◽  
Conjugated Linoleic Acid ◽  
Inflammatory Cytokines ◽  
Amyloid Β ◽  
Amyloid Β Protein ◽  
Β Protein ◽  
Anti Inflammatory ◽  
The Brain

AbstractConjugated linoleic acid (CLA) is an isomer of linoleic acid (LA). The predominant dietary CLA is cis-9, trans-11-CLA (c-9, t-11-CLA), which constitutes up to ~ 90% of total CLA and is thought to be responsible for the positive health benefits associated with CLA. However, the effects of c-9, t-11-CLA on Alzheimer’s disease (AD) remain to be elucidated. In this study, we investigated the effect of dietary intake of c-9, t-11-CLA on the pathogenesis of an AD mouse model. We found that c-9, t-11-CLA diet-fed AD model mice significantly exhibited (1) a decrease in amyloid-β protein (Aβ) levels in the hippocampus, (2) an increase in the number of microglia, and (3) an increase in the number of astrocytes expressing the anti-inflammatory cytokines, interleukin-10 and 19 (IL-10, IL-19), with no change in the total number of astrocytes. In addition, liquid chromatography–tandem mass spectrometry (LC–MS/MS) and gas chromatographic analysis revealed that the levels of lysophosphatidylcholine (LPC) containing c-9, t-11-CLA (CLA-LPC) and free c-9, t-11-CLA were significantly increased in the brain of c-9, t-11-CLA diet-fed mice. Thus, dietary c-9, t-11-CLA entered the brain and appeared to exhibit beneficial effects on AD, including a decrease in Aβ levels and suppression of inflammation.

scholarly journals Early-onset and Robust Cerebral Microvascular Accumulation of Amyloid β-Protein in Transgenic Mice Expressing Low Levels of a Vasculotropic Dutch/Iowa Mutant Form of Amyloid β-Protein Precursor

2004 ◽  
Vol 279 (19) ◽  
pp. 20296-20306 ◽  
Author(s):  
Judianne Davis ◽  
Feng Xu ◽  
Rashid Deane ◽  
Galina Romanov ◽  
Mary Lou Previti ◽  
...  
Keyword(s):  
Early Onset ◽  
Amyloid Β ◽  
Enzyme Linked Immunosorbent Assay ◽  
Mutant Form ◽  
Amyloid Β Protein ◽  
Pathological Feature ◽  
High Association ◽  
Cerebral Microvessels ◽  
Β Protein ◽  
The Brain

Cerebrovascular deposition of amyloid β-protein (Aβ) is a common pathological feature of Alzheimer's disease and related disorders. In particular, the Dutch E22Q and Iowa D23N mutations in Aβ cause familial cerebrovascular amyloidosis with abundant diffuse amyloid plaque deposits. Both of these charge-altering mutations enhance the fibrillogenic and pathogenic properties of Aβin vitro. Here, we describe the generation of several transgenic mouse lines (Tg-SwDI) expressing human neuronal Aβ precursor protein (AβPP) harboring the Swedish K670N/M671L and vasculotropic Dutch/Iowa E693Q/D694N mutations under the control of the mouse Thy1.2 promoter. Tg-SwDI mice expressed transgenic human AβPP only in the brain, but at levels below those of endogenous mouse AβPP. Despite the paucity of human AβPP expression, quantitative enzyme-linked immunosorbent assay measurements revealed that Tg-SwDI mice developed early-onset and robust accumulation of Aβ in the brain with high association with isolated cerebral microvessels. Tg-SwDI mice exhibited striking perivascular/vascular Aβ deposits that markedly increased with age. The vascular Aβ accumulations were fibrillar, exhibiting strong thioflavin S staining, and occasionally presented signs of microhemorrhage. In addition, numerous largely diffuse, plaque-like structures were observed starting at 3 months of age.In vivotransport studies demonstrated that Dutch/Iowa mutant Aβ was more readily retained in the brain compared with wild-type Aβ. These results with Tg-SwDI mice demonstrate that overexpression of human AβPP is not required for early-onset and robust accumulation of both vascular and parenchymal Aβ in mouse brain.

Immunization of Alzheimer model mice with adenovirus vectors encoding amyloid β-protein and GM-CSF reduces amyloid load in the brain

2004 ◽  
Vol 370 (2-3) ◽  
pp. 218-223 ◽  
Author(s):  
Hong-Duck Kim ◽  
Fan-Kun Kong ◽  
Yunpeng Cao ◽  
Terry L. Lewis ◽  
Helen Kim ◽  
...  
Keyword(s):  
Amyloid Β ◽  
Amyloid Β Protein ◽  
Gm Csf ◽  
Β Protein ◽  
Amyloid Load ◽  
Adenovirus Vectors ◽  
The Brain

Multicomponent Training Prevents Memory Deficit Related to Amyloid-β Protein-Induced Neurotoxicity

2021 ◽  
pp. 1-12
Author(s):  
Caroline Bitencourt Soares ◽  
Leticia Rossi Daré ◽  
Karine Ramires Lima ◽  
Luiza Freitas Lopes ◽  
Alexandre Garcia dos Santos ◽  
...  
Keyword(s):  
Recognition Memory ◽  
Physical Exercise ◽  
Amyloid Β ◽  
Memory Deficits ◽  
Amyloid Β Peptide ◽  
Amyloid Β Protein ◽  
Β Protein ◽  
Cognitive Exercise ◽  
The Brain

Background: Alzheimer’s disease (AD) is characterized by the accumulation of the amyloid-β peptide in the brain, leading to early oxidative stress and neurotoxicity. It has been suggested that physical exercise could be beneficial in preventing AD, but studies with multicomponent training are scanty. Objective: Verify the effects of multicomponent exercise training to prevent deficits in recognition memory related to Aβ neurotoxicity. Methods: We subjected Wistar rats to multicomponent training (including aerobic and anaerobic physical exercise and cognitive exercise) and then infused amyloid-β peptide into their hippocampus. Results: We show that long-term multicomponent training prevents the amyloid-β-associated neurotoxicity in the hippocampus. It reduces hippocampal lipid peroxidation, restores antioxidant capacity, and increases glutathione levels, finally preventing recognition memory deficits. Conclusion: Multicomponent training avoids memory deficits related to amyloid-β neurotoxicity on an animal model.

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