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Analysis of Brain Protein Stability Changes in Mouse Models of Alzheimer’s Disease

ABSTRACT: . This study employed different mass spectrometry-based proteomic methods to characterize Alzheimer's Disease (AD) research by examining protein folding and stability in mouse models, offering a fresh perspective beyond traditional protein expression level analysis. Stability of Proteins from Rates of Oxidation (SPROX), Thermal Proteome Profiling (TPP), and Limited Proteolysis (LiP) are used to profile protein stability and conformational change in the hippocampus tissue cell lysates between wild type (n=7) and 5XFAD transgenic (n=7) mice at two time points (t1=2-month, t2=8-month).

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Brain

DISEASE(S): Alzheimer's Disease

SUBMITTER: Yun Tang

LAB HEAD: Michael C. Fitzgerald

PROVIDER: PXD051155 | Pride | 2025-10-13

REPOSITORIES: Pride

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			Action	DRS
	2mo-En-1.raw	Raw
	2mo-En-2.raw	Raw
	2mo-En-3.raw	Raw
	2mo-En.msf	Msf
	2mo-LiP.msf	Msf

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Publications

Analysis of Brain Protein Stability Changes in a Mouse Model of Alzheimer's Disease.

Tang Yun Y Park Hye-Jin HJ Li Shengyu S Fitzgerald Michael C MC

Journal of proteome research 20240918 10

The stability of proteins from rates of oxidation (SPROX), thermal proteome profiling (TPP), and limited proteolysis (LiP) techniques were used to profile the stability of ∼2500 proteins in hippocampus tissue cell lysates from 2- and 8-months-old wild-type (C57BL/6J; <i>n</i> = 7) and transgenic (5XFAD; <i>n</i> = 7) mice with five Alzheimer's disease (AD)-linked mutations. Approximately 200-500 protein hits with AD-related stability changes were detected by each technique at each age point. The ...[more]

PMID: 39292827

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Project description:Described here is the application of thermodynamic stability measurements to study age-related differences in the protein folding and stability of proteins in a rodent model of ageing. Using the Stability of Proteins from Rates of Oxidation (SPROX) technique the thermodynamic stability profiles were generated for 807 proteins in brain cell lystaes from mice, aged 6- (n=7) and 18-months (n=9). The biological variability of the protein stability measurements was low and within the experimental error of SPROX. A total of 83 protein hits were detected with age-related stability differences in the brain samples. Remarkably, the large majority of the brain protein hits were destabilized in the old mice, and the hits were enriched in proteins that have slow turnover rates (p <0.07). Furthermore, 70% of the hits have been previously linked to ageing or age-related diseases. These results help validate the use of thermodynamic stability measurements to capture relevant age-related proteomic changes, and they establish a new biophysical link between these proteins and ageing.

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