L-3-n-Butylphthalide Improves Cognitive Impairment and Reduces Amyloid- in a Transgenic Model of Alzheimer's Disease

• DOI: 10.1523/jneurosci.0340-10.2010
• Publication Date: 2010-06-16T20:30:32Z
• Authors: Y. Peng; J. Sun; S. Hon; A. N. Nylander; W. Xia; Y. Feng; X. Wang; C. A. Lemere
• Keywords: Amyloid (mycology)

Alzheimer9s disease (AD) is an age-related, progressive neurodegenerative disorder that occurs gradually and results in memory, behavior, personality changes. l-3-<i>n</i>-butylphthalide (l-NBP), extract from seeds of <i>Apium graveolens Linn</i> (Chinese celery), has been demonstrated to have neuroprotective effects on ischemic, vascular dementia, amyloid-β (Aβ)-infused animal models. In the current study, we examined l-NBP learning memory a triple-transgenic AD mouse model (3xTg-AD) develops both plaques tangles with aging, as well cognitive deficits. Ten-month-old 3xTg-AD mice were given 15 mg/kg by oral gavage for 18 weeks. treatment significantly improved deficits, long-term spatial compared vehicle control treatment. reduced total cerebral Aβ plaque deposition lowered levels brain homogenates but had no effect fibrillar plaques, suggesting preferential removal diffuse deposits. Furthermore, found markedly enhanced soluble amyloid precursor protein secretion (αAPPs), α-secretase, PKCα expression steady-state full-length APP. Thus, may direct APP processing toward non-amyloidogenic pathway preclude formation mice. The regulating was further confirmed neuroblastoma SK-N-SH cells overexpressing wild-type human APP₆₉₅ (SK-N-SH APPwt). also glial activation oxidative stress shows promising preclinical potential multitarget drug prevention and/or disease.