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Analysis of Brain Protein Stability Changes in Mouse Models of Normal Aging and α-Synucleinopathy Reveals Age- and Disease-Related Differences.

Publication ,  Journal Article
Ma, R; Johnson, JHR; Tang, Y; Fitzgerald, MC
Published in: Journal of proteome research
November 2021

Here, we utilize the stability of proteins from rates of oxidation (SPROX) technique, to profile the thermodynamic stabilities of proteins in brain tissue cell lysates from Huα-Syn(A53T) transgenic mice at three time points including at 1 month (n = 9), at 6 months (n = 7), and at the time (between 9 and 16 months) a mouse became symptomatic (n = 8). The thermodynamic stability profiles generated here on 332 proteins were compared to thermodynamic stability profiles generated on the same proteins from similarly aged wild-type mice using a two-way unbalanced analysis of variance (ANOVA) analysis. This analysis identified a group of 22 proteins with age-related protein stability changes and a group of 11 proteins that were differentially stabilized in the Huα-Syn(A53T) transgenic mouse model. A total of 9 of the 11 proteins identified here with disease-related stability changes have been previously detected in human cerebral spinal fluid and thus have potential utility as biomarkers of Parkinson's disease (PD). The differential stability observed for one protein, glutamate decarboxylase 2 (Gad2), with an age-related change in stability, was consistent with the differential presence of a known, age-related truncation product of this protein, which is shown here to have a higher folding stability than full-length Gad2. Mass spectrometry data were deposited at ProteomeXchange (PXD016985).

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Published In

Journal of proteome research

DOI

EISSN

1535-3907

ISSN

1535-3893

Publication Date

November 2021

Volume

20

Issue

11

Start / End Page

5156 / 5168

Related Subject Headings

  • alpha-Synuclein
  • Synucleinopathies
  • Protein Stability
  • Mice, Transgenic
  • Mice
  • Disease Models, Animal
  • Brain
  • Biochemistry & Molecular Biology
  • Animals
  • Aging
 

Citation

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Ma, R., Johnson, J. H. R., Tang, Y., & Fitzgerald, M. C. (2021). Analysis of Brain Protein Stability Changes in Mouse Models of Normal Aging and α-Synucleinopathy Reveals Age- and Disease-Related Differences. Journal of Proteome Research, 20(11), 5156–5168. https://doi.org/10.1021/acs.jproteome.1c00653
Ma, Renze, Julia H. R. Johnson, Yun Tang, and Michael C. Fitzgerald. “Analysis of Brain Protein Stability Changes in Mouse Models of Normal Aging and α-Synucleinopathy Reveals Age- and Disease-Related Differences.Journal of Proteome Research 20, no. 11 (November 2021): 5156–68. https://doi.org/10.1021/acs.jproteome.1c00653.
Ma R, Johnson JHR, Tang Y, Fitzgerald MC. Analysis of Brain Protein Stability Changes in Mouse Models of Normal Aging and α-Synucleinopathy Reveals Age- and Disease-Related Differences. Journal of proteome research. 2021 Nov;20(11):5156–68.
Ma, Renze, et al. “Analysis of Brain Protein Stability Changes in Mouse Models of Normal Aging and α-Synucleinopathy Reveals Age- and Disease-Related Differences.Journal of Proteome Research, vol. 20, no. 11, Nov. 2021, pp. 5156–68. Epmc, doi:10.1021/acs.jproteome.1c00653.
Ma R, Johnson JHR, Tang Y, Fitzgerald MC. Analysis of Brain Protein Stability Changes in Mouse Models of Normal Aging and α-Synucleinopathy Reveals Age- and Disease-Related Differences. Journal of proteome research. 2021 Nov;20(11):5156–5168.
Journal cover image

Published In

Journal of proteome research

DOI

EISSN

1535-3907

ISSN

1535-3893

Publication Date

November 2021

Volume

20

Issue

11

Start / End Page

5156 / 5168

Related Subject Headings

  • alpha-Synuclein
  • Synucleinopathies
  • Protein Stability
  • Mice, Transgenic
  • Mice
  • Disease Models, Animal
  • Brain
  • Biochemistry & Molecular Biology
  • Animals
  • Aging