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Updated: Dec 25, 2025
Isolation of Intermediate Filament Proteins from Multiple Mouse Tissues to Study Aging-associated Post-translational Modifications
Published on: May 18, 2017
Cytoplasmic mislocalization and mitochondrial colocalization of TDP-43 are common features between normal aged and
Pichet Termsarasab1, Thananan Thammongkolchai2, Ju Gao1
1Department of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA.
Impact Statement:
Despite increasing evidence implicating the important role of TDP-43 in the pathogenesis of a wide range of age-related neurodegenerative diseases, there is limited study of TDP-43 proteinopathy and its association with mitochondria during normal aging. Our findings of cytoplasmic accumulation of TDP-43 that is highly colocalized with mitochondria in neurons in selective brain regions in young animals in the absence of neuronal loss provide a novel insight into the development of TDP-43 proteinopathy and its contribution to neuronal loss.
Insights
TDP-43 proteinopathy, linked to neurodegenerative diseases, was studied in aging brains. Cytoplasmic TDP-43 accumulation near mitochondria in young neurons offers new insights into disease development and neuronal loss.
Area of Science:
- Neuroscience
- Cell Biology
- Pathology
Background:
- TDP-43 is implicated in neurodegenerative diseases.
- Limited research exists on TDP-43 proteinopathy and mitochondria during normal aging.
Purpose of the Study:
- Investigate TDP-43 proteinopathy and its mitochondrial association in normal aging.
- Understand the early stages of TDP-43 proteinopathy and its contribution to neuronal loss.
Main Methods:
- Examined TDP-43 protein localization in neurons.
- Assessed TDP-43 colocalization with mitochondria in specific brain regions.
- Evaluated neuronal loss in young animal models.
Main Results:
- Observed cytoplasmic accumulation of TDP-43 in neurons.
- Found significant colocalization of TDP-43 with mitochondria.
- Detected these changes in young animals without neuronal loss.
Conclusions:
- Early TDP-43 accumulation near mitochondria occurs in normal aging.
- This provides novel insights into TDP-43 proteinopathy development.
- Suggests a potential mechanism contributing to future neuronal loss.
