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Detection of Disease-associated α-synuclein by Enhanced ELISA in the Brain of Transgenic Mice Overexpressing Human A53T Mutated α-synuclein
Published on: May 30, 2015
Tau phosphorylation increases in symptomatic mice overexpressing A30P alpha-synuclein
M Frasier1, M Walzer, L McCarthy
1Department of Pharmacology, Loyola University Medical Center, Maywood, IL 60153, USA.
Experimental Neurology
|March 10, 2005
Summary
Mice with alpha-synuclein buildup show abnormal tau phosphorylation, suggesting alpha-synuclein pathology may trigger early tau changes in Parkinson disease (PD). This links two key protein pathologies in neurodegenerative diseases.
Area of Science:
- Neuroscience
- Molecular Biology
- Pathology
Background:
- Parkinson disease (PD) is linked to alpha-synuclein aggregation.
- Emerging evidence suggests tau pathology may also play a role in PD.
- The relationship between alpha-synuclein and tau pathology requires further investigation.
Purpose of the Study:
- To investigate the link between alpha-synuclein aggregation and tau phosphorylation in a mouse model.
- To determine if alpha-synuclein pathology precedes or coincides with tau changes.
- To explore the molecular mechanisms connecting alpha-synuclein and tau pathology.
Main Methods:
- Utilized a mouse model overexpressing mutant A30P alpha-synuclein.
- Employed immunoblotting and immunocytochemistry with PHF-1 and AT8 antibodies.
- Assessed levels of phosphorylated c-jun kinase (JNK).
Main Results:
- Mice overexpressing A30P alpha-synuclein exhibited abnormal tau phosphorylation.
- Enhanced tau phosphorylation occurred in symptomatic mice with abundant aggregated alpha-synuclein.
- Increased phosphorylated JNK levels were observed, correlating with alpha-synuclein aggregation and tau phosphorylation.
Conclusions:
- Alpha-synuclein pathology in mice is associated with abnormal tau phosphorylation.
- These findings suggest alpha-synuclein pathology can initiate early pathological tau changes.
- The stress kinase JNK may mediate the link between alpha-synuclein and tau pathology in PD.
