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Applications of electron paramagnetic resonance to studies of neurological disease

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Abstract

Electron paramagnetic resonance spectroscopy (EPR) has the potential to give much detail on the structure of the paramagnetic transition ion coordination sites, principally of Cu2+, in a number of proteins associated with central nervous system diseases. Since these sites have been implicated in misfolding/mis-oligomerisation events associated with neurotoxic molecular species and/or the catalysis of damaging redox reactions in neurodegeneration, an understanding of their structure is important to the development of therapeutic agents. Nevertheless EPR, by its nature an in vitro technique, has its limitations in the study of such complex biochemical systems involving self-associating proteins that are sensitive to their chemical environment. These limitations are at the instrumental and theoretical level, which must be understood and the EPR data interpreted in the light of other biophysical and biochemical studies if useful conclusions are to be drawn.

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Abbreviations

α-Sn:

α-synuclein

AD:

Alzheimer’s disease

APP:

Amyloid precursor protein

DEPC:

Diethylpyrocarbonate

EPR:

Electron paramagnetic resonance

ENDOR:

Electron nuclear double resonance

ESEEM:

Electron spin echo envelope modulation

ESR:

Electron spin resonance

EXAFS:

Extended X-ray absorption fine structure

NMR:

Nuclear magnetic resonance

PB:

Scheme of Peisach and Blumberg (1974)

PD:

Parkinson’s disease

PrP:

Prion protein

ROS:

Reactive oxygen species

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Correspondence to John F. Boas.

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Australian Society for Biophysics Special Issue: Metals and Membranes in Neuroscience, held in Melbourne on 11 July 2007.

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Boas, J.F., Drew, S.C. & Curtain, C.C. Applications of electron paramagnetic resonance to studies of neurological disease. Eur Biophys J 37, 281–294 (2008). https://doi.org/10.1007/s00249-008-0261-8

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