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Updated: May 8, 2026
09:29
Isolation of Intermediate Filament Proteins from Multiple Mouse Tissues to Study Aging-associated Post-translational Modifications
Published on: May 18, 2017
Brain site-specific proteome changes in aging-related dementia
Arulmani Manavalan1, Manisha Mishra, Lin Feng
1School of Biological Sciences, Nanyang Technological University, Singapore, Singapore.
Experimental & Molecular Medicine
|September 7, 2013
Summary
Researchers identified key protein changes in the brain related to Alzheimer's disease (AD) and normal aging. These findings highlight potential biomarkers and suggest a weakened ubiquitin proteasome system (UPS) contributes to neurodegeneration in AD.
Area of Science:
- Neuroscience
- Proteomics
- Molecular Biology
Background:
- Aging is associated with cognitive decline and increased risk of neurodegenerative diseases like Alzheimer's disease (AD).
- Understanding the brain's site-specific molecular changes during aging and AD is crucial for identifying therapeutic targets.
- Proteomic alterations in specific brain regions may underlie age-related neurodegeneration.
Purpose of the Study:
- To investigate the brain site-specific proteomic signature of senescence in physiologically aged versus AD brains.
- To compare proteomic differences in the hippocampus (Hp), parietal cortex (pCx), and cerebellum (Cb) to understand aging-related neurodegeneration mechanisms.
- To identify novel protein biomarkers and molecular pathways involved in AD pathogenesis.
Main Methods:
- Utilized isobaric tag for relative and absolute quantitation (iTRAQ) with 2D-LC-MS/MS for brain-specific proteomic analysis.
- Analyzed proteomic profiles from hippocampus, parietal cortex, and cerebellum of AD brains.
- Performed Ingenuity Pathway Analysis (IPA) for network and pathway elucidation.
Main Results:
- Identified 950 proteins in AD brain regions, with 31 significantly altered.
- Differentially regulated proteins are primarily involved in molecular transport, nervous system development, synaptic plasticity, and apoptosis.
- Gelsolin (GSN), Tenascin-R (TNR), and AHNAK were identified as potential novel biomarkers for aging-related neurodegeneration.
- Ubiquitin C (UBC) emerged as a pivotal protein interacting with AD-associated factors, suggesting a role for the reduced ubiquitin proteasome degradation system (UPS) in AD.
Conclusions:
- The study reveals distinct proteomic signatures of senescence in specific brain regions affected by AD.
- Identified potential novel biomarkers (GSN, TNR, AHNAK) for aging-related neurodegeneration.
- Reduced ubiquitin proteasome system (UPS) function is implicated as a causative factor in Alzheimer's disease pathogenesis.
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