Decreased Water Mobility Contributes To Increased α-Synuclein Aggregation.

Area of Science:

• Biochemistry
• Physical Chemistry
• Neuroscience

Background:

• The solvation shell is critical for protein folding and function.
• Its role in protein misfolding and aggregation, particularly in diseases like Parkinson's, remains unclear.

Purpose of the Study:

• To investigate the influence of solvation shell water mobility on the aggregation rate of alpha-synuclein (αSyn).
• To elucidate the mechanisms by which solvent properties affect αSyn aggregation.

Main Methods:

• Studied the aggregation rates of αSyn under varying solvent conditions.
• Utilized NaCl and CsI to modulate solvation shell water mobility.
• Employed D2O as a solvent to assess solvent-driven effects.

Main Results:

• Reduced solvation shell water mobility, induced by NaCl, increased αSyn aggregation rates.
• Increased water mobility, induced by CsI, decreased αSyn aggregation rates.
• Switching to D2O also increased aggregation rates, confirming a solvent effect.
• Increased aggregation correlated with reduced mobility of both water and αSyn, not conformational changes.

Conclusions:

• Solvation shell water mobility is a key determinant of αSyn aggregation rates.
• Reduced mobility of both water and αSyn promotes aggregation by facilitating intermolecular interactions.
• This finding offers new insights into the pathogenesis of Parkinson's disease.