FTIR studies of the similarities between pathology induced protein aggregation in vivo and chemically induced protein aggregation ex vivo
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© 2016 Elsevier B.V.Fourier transform infrared (FTIR) spectroscopy has been well documented to discriminate between protein secondary structures, at the micron scale. This capability has enabled in situ localization of ß-sheet aggregate accumulation within the central nervous system during pathological protein misfolding associated with Prion disease, Amyotrophic Lateral Sclerosis, Huntington's Disease, Alzheimer's' Disease, and Parkinson's Disease. In addition to the above diseases, similar spectral alterations occurring over the range ~1625-1630cm-1 have been reported in other biological systems, including inclusion body formation within bacteria and during the formation of high molecular weight protein aggregates via protein oxidation and denaturation. Thus, the characteristic spectral alterations to the amide-I band observed during protein misfolding in neurological disorders are likely not specific to these diseases, but rather, reflect an aggregated protein end point, which can result from a range of biochemical events. For example, a common pathogenic component of many neurological conditions is oxidative stress, protein oxidation and altered ion homeostasis, which have the potential to denature proteins and promote the formation of high molecular weight aggregates.Oxidative stress is a generic feature of neurodegenerative diseases and also occurs during neurodegenerative conditions, such as stroke, multiple sclerosis, epilepsy and cerebral malaria. These neuropathological disorders do not have an established protein misfolding pathology, in contrast to Prion disease, Amyotrophic Lateral Sclerosis, Huntington's Disease, Alzheimer's' Disease, which do have an established protein misfolding pathology. Interestingly, recent studies using FTIR have confirmed the presence of protein aggregates within the central nervous system during stroke, cerebral malaria, epilepsy, multiple sclerosis. Such reports suggest FTIR spectroscopy may be a highly valuable research tool to study protein aggregation as a marker of oxidative stress and neurodegeneration in many diseases, not just those with a characteristic pathology for protein misfolding. This manuscript extends the recent literature and reports further characterization of the alterations to the amide I band that result from ubiquitous . ex vivo protein aggregation in cerebral tissue. The new data presented highlights that the spectroscopic alterations to the amide I band often reported for amyloid-ß plaques in Alzheimer's disease, are spectroscopically very similar to spectroscopic alterations observed during ischemia induced neurodegeneration (stroke) and . ex vivo induced protein aggregation. As such, this study further validates FTIR as a useful platform to study protein aggregation in neurological disorders, including those not characterized by protein misfolding pathology.
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