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Increased amyloidogenic secretion in cerebellar granule cells undergoing apoptosis
C Galli1, A Piccini, M T Ciotti
1Istituto di Neurobiologia, Consiglio Nazionale delle Ricerche, Via K. Marx 43, 00137 Rome, Italy. galli@biocell.irmkant.rm.cnr.it
Summary
Neuronal apoptosis significantly increases amyloid beta protein (Abeta) secretion, suggesting that neuronal damage may elevate Abeta production. This study investigated Abeta metabolism during apoptosis.
Area of Science:
- Neuroscience
- Molecular Biology
- Cell Biology
Background:
- Neuronal damage may alter amyloid beta protein (Abeta) metabolism.
- Amyloid precursor protein (APP) processing is central to Abeta production.
Purpose of the Study:
- To investigate Abeta secretion and APP processing in an in vitro model of neuronal apoptosis.
- To determine if neuronal apoptosis affects Abeta production.
Main Methods:
- Primary rat cerebellar granule neurons were induced into apoptosis.
- Metabolic labeling with [35S]methionine and immunoprecipitation were used to analyze Abeta and APP.
- SDS/PAGE and densitometry quantified protein levels.
- Immunofluorescence visualized Abeta distribution.
Main Results:
- Intracellular full-length APP levels remained unchanged post-apoptosis.
- Depolarization-stimulated Abeta secretion increased 3-fold in apoptotic neurons.
- The ratio of beta-secretase-cleaved APP (beta-APPs) to alpha-secretase-cleaved APP (alpha-APPs) increased.
Conclusions:
- Neuronal apoptosis is linked to increased beta-secretase cleavage of APP.
- Elevated Abeta production may result from neuronal damage in various conditions.
- Abeta redistribution within apoptotic cells was observed.