+ Site Statistics
References:
54,258,434
Abstracts:
29,560,870
PMIDs:
28,072,757
+ Search Articles
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ PDF Full Text
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Translate
+ Recently Requested

GEPT extract reduces Abeta deposition by regulating the balance between production and degradation of Abeta in APPV717I transgenic mice



GEPT extract reduces Abeta deposition by regulating the balance between production and degradation of Abeta in APPV717I transgenic mice



Current Alzheimer Research 6(2): 118-131



Accumulation of beta-amyloid peptide (Abeta) in the brain is a primary influence driving Alzheimer's disease (AD) pathogenesis. The disease process, including formation of neurofibrillary tangles containing tau protein, is proposed to result from an imbalance between production and clearance of Abeta. A major therapeutic strategy for AD should be to decrease deposition of Abeta by the inhibition of its production and the facilitation of its degradation. Hence, the primary aim of this study was to investigate effects of GEPT, a combination of herbal extracts, on Abeta levels, beta- and gamma-secretases substrate (BACE1 and PS1, respectively) associated with production of Abeta, and insulin-degrading enzyme (IDE) and neprilysin (NEP) related to degradation of Abeta in the brain. Three-month-old-male APPV717I mice were randomly divided into five groups (n=6 per group): (i) APP mice alone were given distilled water, (ii) APP donepezil mice were treated with donepezil (0.92 mg/kg/d), and (iii-v) APP mice treated with GEPT low dose (0.75 g/kg/d), middle dose (1.5 g/kg/d), and large dose (3.0 g/kg/d) for 8 months. Three-month-old-male C57BL/6J mice (n=6) for vehicle were given distilled water for 8 months. Immunohistochemistry and Western blot analysis were used in determining amyloid precursor protein (APP), Abeta1-42, BACE1, PS1, IDE and NEP in hippocampal CA1 region and hippocampal tissue homogenates. Expression level of Abeta1-42 in the large GEPT dose was significantly lower than those in APP alone or APP treated with donepezil, and decreased to the level of vehicle mice. Similarly, a ratio calculated from the densitometric measures of Abeta1-42 protein/beta-actin in the large dose also was significantly lower than those in APP mice alone or APP mice treated with donepezil, and even reduced to the level of vehicle mice. Expression of PS1 in the large GEPT dose was significantly lower than that of APP mice alone and decreased to those in vehicle mice as well. A decreased level of BACE1 appeared, respectively, in APP mice treated with the large GEPT dose or donepezil but was still much greater than the level of vehicle mice. In contrast, NEP and IDE showed a significantly higher expression in APP mice treated with either the large dose or the middle dose of GEPT compared to APP mice alone or donepezil, and were even increased in level compared to vehicle mice. The combination of GEPT extracts can reduce levels of endogenous Abeta peptide in APPV717I transgenic mice through the inhibition of PS1 activity rather than BACE1 and the promotion of IDE and NEP activity. Lower-expression of PS1 and over-expression of IDE or NEP may be helpful in potentially lowering brain Abeta levels in subjects with AD, and hence GEPT appears to offer potential that should be explored in AD.

(PDF emailed within 1 workday: $29.90)

Accession: 053341005

Download citation: RISBibTeXText

PMID: 19355846


Related references

p75NTR regulates Abeta deposition by increasing Abeta production but inhibiting Abeta aggregation with its extracellular domain. Journal of Neuroscience 31(6): 2292-2304, 2011

Vaccination with Abeta-displaying virus-like particles reduces soluble and insoluble cerebral Abeta and lowers plaque burden in APP transgenic mice. Journal of Immunology 182(12): 7613-7624, 2009

Vaccination with Abeta displaying virus-like particles reduces soluble and insoluble cerebral Abeta and lowers plaque burden in APP transgenic mice. Alzheimer's & Dementia 5(4): P418-P419, 2009

Behavioral assessment of Alzheimer's transgenic mice following long-term Abeta vaccination: task specificity and correlations between Abeta deposition and spatial memory. Dna and Cell Biology 20(11): 737-744, 2002

Vaccination of Alzheimer's model mice with adenovirus vector containing quadrivalent foldable Abeta(1-15) reduces Abeta burden and behavioral impairment without Abeta-specific T cell response. Journal of the Neurological Sciences 272(1-2): 87-98, 2008

Estrogen reduces Abeta peptide levels and amyloid deposition in APP transgenic mice. Journal of Neurochemistry 81(Supplement 1): 82, 2002

Environmental enrichment reduces Abeta levels and amyloid deposition in transgenic mice. Cell 120(5): 701-713, 2005

IBUPROFEN PREFERENTIALLY REDUCES Abeta DEPOSITION IN AMYLOID PRECURSOR PROTEIN TRANSGENIC MICE. Society for Neuroscience Abstract Viewer & Itinerary Planner : Abstract No 483 4, 2002

Effects of non-steroidal anti-inflammatory drugs on Abeta deposition in Abeta(1-42) transgenic C. elegans. Brain Research 1295: 186-191, 2009

E22Q-mutant Abeta peptide (AbetaDutch) increases vascular but reduces parenchymal Abeta deposition. American Journal of Pathology 174(3): 722-726, 2009

Angiotensin-converting enzyme converts amyloid beta-protein 1-42 (Abeta(1-42)) to Abeta(1-40), and its inhibition enhances brain Abeta deposition. Journal of Neuroscience 27(32): 8628-8635, 2007

Systemic administration of Abeta mAb reduces retinal deposition of Abeta and activated complement C3 in age-related macular degeneration mouse model. Plos One 8(6): E65518, 2014

Early vitamin E supplementation in young but not aged mice reduces Abeta levels and amyloid deposition in a transgenic model of Alzheimer's disease. Faseb Journal 18(2): 323-325, 2003

Number of Abeta immunizations in APP+PS1 transgenic mice influences titers, Abeta load and microglial activation. Society for Neuroscience Abstracts 27(2): 1718, 2001

Transgenic mice expressing BRI-Abeta fusion proteins selectively overexpress Abeta42 and other Abeta peptides. Society for Neuroscience Abstracts 27(2): 2287, 2001