NIH Research Festival
Parkinson’s disease (PD) is a neurodegenerative movement disorder affecting one in 100 people over the age of 60. alpha-Synuclein (alpha-syn) is a small protein known to be linked to PD etiology, and though a clear biological role has not been established, aggregated forms of alpha-syn in cellular inclusions known as Lewy bodies are a diagnostic hallmark of the disease. Structurally, alpha-syn is disordered in solution, but takes a helical form when membrane bound and is beta-sheet in its amyloid, disease-related state. Evidence suggests alpha-syn-membrane interactions can lead to cell death and understanding these interactions will shed light on a relationship to disease. Raman spectroscopy is a powerful approach that can offer new insights into the conformational dynamics and aggregation of alpha-syn within a cellular environment. Here, we couple a Raman spectrometer to an epifluorescence microscope in order to monitor specific stretching frequencies that provide protein structural information, while simultaneously collecting spatial information and revealing a molecular view of alpha-syn aggregation not achievable with fluorescence microscopy alone. In this work, we will observe the aggregation of isotopically-labeled alpha-syn and track the amide-I stretching frequency in a spectral region free of endogenous protein signals as a signature for protein conformational changes. This in vitro study will establish an experimental foundation that will be extended for characterizing the intracellular conformation and aggregation state of alpha-syn in vivo. Importantly, this work will reveal structural information that may lead to an improved understanding of the structure-function relationship of alpha-syn in the disease pathway of PD.
Scientific Focus Area: Biomedical Engineering and Biophysics
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