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Effects of Trehalose on Thermodynamic Properties of Alpha-synuclein Revealed through Synchrotron Radiation Circular Dichroism.

Ruzza P, Hussain R, Biondi B, Calderan A, Tessari I, Bubacco L, Siligardi G - Biomolecules (2015)

Bottom Line: Many neurodegenerative diseases, including Huntington's, Alzheimer's and Parkinson's diseases, are characterized by protein misfolding and aggregation.Our study indicated that a low trehalose concentration stabilized α-synuclein folding much better than at high concentration by blocking in vitro α-synuclein's polymerisation.These results suggested that trehalose could be associated with other drugs leading to a new approach for treating Parkinson's and other brain-related diseases.

View Article: PubMed Central - PubMed

Affiliation: Institute of Biomolecular Chemistry of CNR, Padua Unit, Padua 35131, Italy. paolo.ruzza@cnr.it.

ABSTRACT
Many neurodegenerative diseases, including Huntington's, Alzheimer's and Parkinson's diseases, are characterized by protein misfolding and aggregation. The capability of trehalose to interfere with protein misfolding and aggregation has been recently evaluated by several research groups. In the present work, we studied, by means of synchrotron radiation circular dichroism (SRCD) spectroscopy, the dose-effect of trehalose on α-synuclein conformation and/or stability to probe the capability of this osmolyte to interfere with α-synuclein's aggregation. Our study indicated that a low trehalose concentration stabilized α-synuclein folding much better than at high concentration by blocking in vitro α-synuclein's polymerisation. These results suggested that trehalose could be associated with other drugs leading to a new approach for treating Parkinson's and other brain-related diseases.

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Far-UV SRCD spectra of α-synuclein alone (a) or in presence of 10 mM (b) or 100 mM (c) trehalose at different temperature (indicated). α-Synuclein concentration was 0.36 mg/mL in PBS buffer, pH 7.4.
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biomolecules-05-00724-f003: Far-UV SRCD spectra of α-synuclein alone (a) or in presence of 10 mM (b) or 100 mM (c) trehalose at different temperature (indicated). α-Synuclein concentration was 0.36 mg/mL in PBS buffer, pH 7.4.

Mentions: The trehalose concentration effect on the stability of aqueous α-synuclein in its disordered native state was assessed by thermal denaturation experiments (Figure 3). Qualitatively the observed CD changes as a function of temperature from 5 °C to 90 °C at 5 °C intervals were similar with a decreased intensity of the negative band at about 197 nm and an increased intensity of the negative shoulder at about 220 nm. Quantitatively, however, the rate of changes were significantly different showing a reduced rate with 10 mM trehalose than that of α-synuclein but an increased one with 100 mM trehalose (Figure 4). The melting process was reversible with 10 mM and almost for 100 mM trehalose but not for α-synuclein (Figure 3) highlighting the different thermodynamic properties induced by trehalose to the protein.


Effects of Trehalose on Thermodynamic Properties of Alpha-synuclein Revealed through Synchrotron Radiation Circular Dichroism.

Ruzza P, Hussain R, Biondi B, Calderan A, Tessari I, Bubacco L, Siligardi G - Biomolecules (2015)

Far-UV SRCD spectra of α-synuclein alone (a) or in presence of 10 mM (b) or 100 mM (c) trehalose at different temperature (indicated). α-Synuclein concentration was 0.36 mg/mL in PBS buffer, pH 7.4.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4496693&req=5

biomolecules-05-00724-f003: Far-UV SRCD spectra of α-synuclein alone (a) or in presence of 10 mM (b) or 100 mM (c) trehalose at different temperature (indicated). α-Synuclein concentration was 0.36 mg/mL in PBS buffer, pH 7.4.
Mentions: The trehalose concentration effect on the stability of aqueous α-synuclein in its disordered native state was assessed by thermal denaturation experiments (Figure 3). Qualitatively the observed CD changes as a function of temperature from 5 °C to 90 °C at 5 °C intervals were similar with a decreased intensity of the negative band at about 197 nm and an increased intensity of the negative shoulder at about 220 nm. Quantitatively, however, the rate of changes were significantly different showing a reduced rate with 10 mM trehalose than that of α-synuclein but an increased one with 100 mM trehalose (Figure 4). The melting process was reversible with 10 mM and almost for 100 mM trehalose but not for α-synuclein (Figure 3) highlighting the different thermodynamic properties induced by trehalose to the protein.

Bottom Line: Many neurodegenerative diseases, including Huntington's, Alzheimer's and Parkinson's diseases, are characterized by protein misfolding and aggregation.Our study indicated that a low trehalose concentration stabilized α-synuclein folding much better than at high concentration by blocking in vitro α-synuclein's polymerisation.These results suggested that trehalose could be associated with other drugs leading to a new approach for treating Parkinson's and other brain-related diseases.

View Article: PubMed Central - PubMed

Affiliation: Institute of Biomolecular Chemistry of CNR, Padua Unit, Padua 35131, Italy. paolo.ruzza@cnr.it.

ABSTRACT
Many neurodegenerative diseases, including Huntington's, Alzheimer's and Parkinson's diseases, are characterized by protein misfolding and aggregation. The capability of trehalose to interfere with protein misfolding and aggregation has been recently evaluated by several research groups. In the present work, we studied, by means of synchrotron radiation circular dichroism (SRCD) spectroscopy, the dose-effect of trehalose on α-synuclein conformation and/or stability to probe the capability of this osmolyte to interfere with α-synuclein's aggregation. Our study indicated that a low trehalose concentration stabilized α-synuclein folding much better than at high concentration by blocking in vitro α-synuclein's polymerisation. These results suggested that trehalose could be associated with other drugs leading to a new approach for treating Parkinson's and other brain-related diseases.

Show MeSH
Related in: MedlinePlus