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Millisecond Hydrogen/Deuterium-Exchange Mass Spectrometry for the Study of Alpha-Synuclein Structural Dynamics Under Physiological Conditions
Published on: June 23, 2022
Mathematical approach to understand the kinetics of alpha-synuclein aggregation: relevance to Parkinson's disease
P Bharathi1, P Nagabhushan, K S J Rao
1Department of Biochemistry and Nutrition, Central Food Technological Research Institute, Mysore 570020, India.
Abstract:
alpha-Synuclein aggregation is a hallmark pathological feature in Parkinson's disease (PD). The conversion of alpha-synuclein from soluble monomer to insoluble aggregates through the toxic oligomeric intermediates underlie the neurodegeneration associated with PD. Redox active metal ions such as iron (Fe) and copper (Cu) are known to enhance alpha-synuclein fibrillogenesis. In the present study, we have implemented mathematical approach to monitor the kinetics of aggregation of alpha-synuclein nucleation and elongation constants based on fluorescence studies. In this pretext, we have implemented mathematical simulations like self and absolute analysis. The mathematical model discussed in this paper is the first of its kind and might prove useful for predicting the drug intervention time to prevent alpha-synuclein aggregation and has future clinical application.
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