Synchrotron-based infrared spectroscopy brings to light the structure of protein aggregates in neurodegenerative diseases

Abstract

The accumulation of misfolded proteins in the form of aggregates characterizes a number of diseases of the central nervous system such as Alzheimer’s disease, Parkinson’s disease, prion diseases, and the diseases of polyglutamine expansion. Recent evidence obtained in vitro and in mice has suggested that protein aggregates are structurally diverse and that their structure largely determines toxicity. The structure of the aggregated proteins in the brain of human patients remains mostly unknown, and we will give here the reasons for which synchrotron-based infrared spectroscopy is emerging as one of the best techniques to access this structure. We will also review the few publications that already exist on the application of synchrotron-based infrared spectroscopy to the study of protein aggregates in human brain. The establishment of a correlation between aggregate structure and neurological toxicity is important not only to understand the aggregation process itself but also in order to specifically target the most toxic structures when searching for prophylactic or therapeutic inhibitors of protein aggregation.

Keywords

• alzheimer
• amyloid
• huntington
• parkinson
• prion