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 ◽  
...  

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.

2002 ◽  
Vol 71 (1) ◽  
pp. 313-322 ◽  
Author(s):  
Fumitaka Oyama ◽  
Naoya Sawamura ◽  
Kimio Kobayashi ◽  
Maho Morishima-Kawashima ◽  
Takashi Kuramochi ◽  
...  

2005 ◽  
Vol 10 (1) ◽  
pp. 1-12 ◽  
Author(s):  
Pancham Bakshi ◽  
Yung-Feng Liao ◽  
Jun Gao ◽  
Jake Ni ◽  
Ross Stein ◽  
...  

Cerebral accumulation of the amyloid β-peptide (Aβ) is believed to play a key role in the pathogenesis of Alzheimer’s disease (AD). Because Aβ is produced from the proteolysis of amyloid β-protein precursor (APP) by β-and γ-secretases, these enzymes are considered important drug targets for AD. The authors have developed a luciferase-based reporter system that can identify new molecules that inhibit APP processing in a high-throughput manner. Such molecules can help in understanding the biology of APP and APP processing and in developing new drug prototypes for AD. In this system, APP is fused on its C-terminus with Gal4-VP16, a chimeric yeast-viral transcription activator, and luciferase is under control of the yeast Gal4 promoter. Compounds that modulate the luciferase signal may affect the secretases directly, interact with modifiers of these proteases, or interact with APP directly. The authors successfully interfaced this assay with a high-throughput screen, testing ~60,000 compounds with diverse chemical structures. In principle, this sensitive, specific, and quantitative assay may be useful for identifying both inhibitors and stimulators of APP processing.( Journal of Biomolecular Screening 2005:1-12)


2014 ◽  
Vol 92 (5) ◽  
pp. 351-355 ◽  
Author(s):  
Hironori Fujiwara ◽  
Junko Kimura ◽  
Masahiro Sakamoto ◽  
Akihito Yokosuka ◽  
Yoshihiro Mimaki ◽  
...  

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.


Nature ◽  
2002 ◽  
Vol 416 (6880) ◽  
pp. 535-539 ◽  
Author(s):  
Dominic M. Walsh ◽  
Igor Klyubin ◽  
Julia V. Fadeeva ◽  
William K. Cullen ◽  
Roger Anwyl ◽  
...  

2001 ◽  
Vol 158 (6) ◽  
pp. 2209-2218 ◽  
Author(s):  
Noriko Oshima ◽  
Maho Morishima-Kawashima ◽  
Haruyasu Yamaguchi ◽  
Masahiro Yoshimura ◽  
Shiro Sugihara ◽  
...  

2011 ◽  
Vol 23 (3) ◽  
pp. 521-535 ◽  
Author(s):  
Luis De Taboada ◽  
Jin Yu ◽  
Salim El-Amouri ◽  
Sebastiano Gattoni-Celli ◽  
Steve Richieri ◽  
...  

2005 ◽  
Vol 7 (2) ◽  
pp. 139-148 ◽  
Author(s):  
Xiao-Ping Shi ◽  
Katherine Tugusheva ◽  
James E. Bruce ◽  
Adam Lucka ◽  
Elizabeth Chen-Dodson ◽  
...  

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