Molecular Spectroscopic Markers of Abnormal Protein Aggregation.

Natalia Wilkosz,Ewelina Lipiec,Sara Seweryn,Michał Czaja,Katarzyna Skirlińska-Nosek,Marek Szymonski,Kamila Sofińska

doi:10.3390/molecules25112498

Natalia Wilkosz, Ewelina Lipiec + Show 5 more

Open Access

https://doi.org/10.3390/molecules25112498

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Abstract

Abnormal protein aggregation has been intensively studied for over 40 years and broadly discussed in the literature due to its significant role in neurodegenerative diseases etiology. Structural reorganization and conformational changes of the secondary structure upon the aggregation determine aggregation pathways and cytotoxicity of the aggregates, and therefore, numerous analytical techniques are employed for a deep investigation into the secondary structure of abnormal protein aggregates. Molecular spectroscopies, including Raman and infrared ones, are routinely applied in such studies. Recently, the nanoscale spatial resolution of tip-enhanced Raman and infrared nanospectroscopies, as well as the high sensitivity of the surface-enhanced Raman spectroscopy, have brought new insights into our knowledge of abnormal protein aggregation. In this review, we order and summarize all nano- and micro-spectroscopic marker bands related to abnormal aggregation. Each part presents the physical principles of each particular spectroscopic technique listed above and a concise description of all spectral markers detected with these techniques in the spectra of neurodegenerative proteins and their model systems. Finally, a section concerning the application of multivariate data analysis for extraction of the spectral marker bands is included.

Highlights

Following the increase of global average life expectancy, the world population has experienced an upsurge in the number of individuals suffering from deadly and debilitating neurodegenerative diseases, such as Alzheimer’s, Parkinson’s, and Huntington’s disorders [1,2,3]
Despite the absence/low intensity of the amide I band in the studies described above, it was confirmed that Tip-enhanced Raman Spectroscopy (TERS) is an efficient tool for investigation of the amyloids secondary structure and for direct verification of the aggregation pathway [118]
The work presented in this review shows the enormous progress in the state of knowledge concerning amyloid aggregation

Summary

Introduction

Following the increase of global average life expectancy, the world population has experienced an upsurge in the number of individuals suffering from deadly and debilitating neurodegenerative diseases, such as Alzheimer’s, Parkinson’s, and Huntington’s disorders [1,2,3]. Bas well as amide bands I‐VII (wavenumbers and assigned vibrations are shown in Table 1) can be species in of amyloid aggregation, as well as fibrils, are represented by a different ratio of individual observed the Raman and infrared spectra of peptides and proteins. The FTIR spectra were collected for amorphous aggregates as well as for fibrils (created at low pH) exposed to pepsin to receive a sample containing only a fibrillar structure with characteristic low frequency band for parallel β-sheets (1618 cm−1 ).

Results

Conclusion