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Dysregulation of Amp-activated Protein Kinase Signaling in Alzheimer's Disease
Başlık:
Dysregulation of Amp-activated Protein Kinase Signaling in Alzheimer's Disease
Yazar:
Wang, Xin, author.
ISBN:
9780355986822
Yazar Ek Girişi:
Fiziksel Tanımlama:
1 electronic resource (71 pages)
Genel Not:
Source: Masters Abstracts International, Volume: 57-06M(E).
Advisors: Tao Ma Committee members: Tao Ma; Shannon Macauley-Rambach; Carol Shively.
Özet:
The etiology of Alzheimer's disease (AD), one of the most grievous neurodegenerative disease, is still unclear despite decades of study and early diagnosis of this disease remains a challenge. Energy metabolic dysfunction has been found to be a distinct characteristic in Alzheimer's disease, and may be the underlying pathogenic mechanism of Alzheimer's disease. AMP-activated protein kinase (AMPK) is a master energy sensor which can sense the ratio of AMP/ATP and regulates catabolic and anabolic pathways to keep the energy metabolism in balance, and has been found to play an important role in the pathogenesis of Alzheimer's disease. AMPK has 3 subunits, the alpha, beta and gamma. The alpha subunit is the catalytic subunit and has 2 isoforms, alpha1 and alpha2. Phosphorylation of alpha subunit determines the activity of AMPK. In this study, I found AMPKalpha2 was dysregulated in a vervet monkey model of Alzheimer's disease, which exhibited AD-like pathologies, biochemical alterations and behaviors. Proteomic studies in this model showed that many of dysregulated proteins were metabolism-related and could be associated with AMPK signaling. I also found level of AMPKalpha1 was significantly deceased in the plasma of AD and mild cognitive impairment (MCI) patients as compared to healthy controls and the efficacy of AMPKalpha1 level in plasma to differentiate patients from controls was relatively high. In summary, this study found that AMPK signaling was dysregulated in a vervet monkey model of Alzheimer's disease, which could be used as a tool for development of therapeutics of Alzheimer's disease, and AMPKalpha1 was significantly decreased in the plasma of AD and MCI patients, indicating that AMPKalpha1 could serve as a biomarker for the early diagnosis of Alzheimer's disease.
Notlar:
School code: 0248
Tüzel Kişi Ek Girişi:
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Yer Numarası | Demirbaş Numarası | Shelf Location | Lokasyon / Statüsü / İade Tarihi |
---|---|---|---|
XX(691995.1) | 691995-1001 | Proquest E-Tez Koleksiyonu | Arıyor... |
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