The Influence of Spin-Labeled Fluorene Compounds on the Assembly and Toxicity of the A? Peptide
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Tartalom: http://real.mtak.hu/20451/
Archívum: MTA Könyvtár
Gyűjtemény: Status = Published


Type = Article
Cím:
The Influence of Spin-Labeled Fluorene Compounds on the Assembly and Toxicity of the A? Peptide
Létrehozó:
Petrlova, Jitka
Kálai, Tamás
Maezawa, Izumi
Altman, Robin
Harishchandra, Ghimire
Hong, Hyun- Seok
Bricarello, Daniel A.
Parikh, Atul N.
Lorigan, Garry A.
Jin, Li-Way
Hideg, Kálmán
Voss, John C.
Dátum:
2012
Téma:
RM Therapeutics. Pharmacology / terápia, gyógyszertan
RS Pharmacy and materia medica / gyógyszerészet, gyógyászati eszközök
Tartalmi leírás:
The deposition and oligomerization of amyloid ? (A?) peptide plays a key role in the pathogenesis of Alzheimer's disease (AD). A? peptide arises from cleavage of the membrane-associated domain of the amyloid precursor protein (APP) by ? and ? secretases. Several lines of evidence point to the soluble A? oligomer (A?O) as the primary neurotoxic species in the etiology of AD. Recently, we have demonstrated that a class of fluorene molecules specifically disrupts the A?O species.
Methodology/Principal Findings
To achieve a better understanding of the mechanism of action of this disruptive ability, we extend the application of electron paramagnetic resonance (EPR) spectroscopy of site-directed spin labels in the A? peptide to investigate the binding and influence of fluorene compounds on A?O structure and dynamics. In addition, we have synthesized a spin-labeled fluorene (SLF) containing a pyrroline nitroxide group that provides both increased cell protection against A?O toxicity and a route to directly observe the binding of the fluorene to the A?O assembly. We also evaluate the ability of fluorenes to target multiple pathological processes involved in the neurodegenerative cascade, such as their ability to block A?O toxicity, scavenge free radicals and diminish the formation of intracellular A?O species.
Conclusions
Fluorene modified with pyrroline nitroxide may be especially useful in counteracting A? peptide toxicity, because they posses both antioxidant properties and the ability to disrupt A?O species.
Típus:
Article
PeerReviewed
Formátum:
text
Azonosító:
Petrlova, Jitka and Kálai, Tamás and Maezawa, Izumi and Altman, Robin and Harishchandra, Ghimire and Hong, Hyun- Seok and Bricarello, Daniel A. and Parikh, Atul N. and Lorigan, Garry A. and Jin, Li-Way and Hideg, Kálmán and Voss, John C. (2012) The Influence of Spin-Labeled Fluorene Compounds on the Assembly and Toxicity of the A? Peptide. PLOS ONE, 7. e35443. ISSN 1932-6203
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