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Endogenous APP derivatives oppositely modulate apoptosis through an autocrine loop.
A Piccini1, M T Ciotti, O V Vitolo
1Istituto di Neurobiologia, Consiglio Nazionale delle Ricerche, Rome, Italy.
Neuroreport
|June 7, 2000
Summary
Amyloid precursor protein (APP) fragments impact neuronal survival. Antibodies targeting amyloid beta (A beta) increased survival, while those targeting alpha-APP decreased it, suggesting a dual role in cell death and survival.
Area of Science:
- Neuroscience
- Molecular Biology
- Cell Biology
Background:
- Apoptosis in cerebellar granule cells is linked to amyloid precursor protein (APP) processing.
- This processing shift increases amyloid beta-protein (A beta) secretion.
Purpose of the Study:
- To investigate the relationship between APP metabolite secretion and neuronal degeneration.
- To explore the autocrine loop mechanism of APP metabolites in modulating neuronal survival.
Main Methods:
- Treatment of rat cerebellar granule cells with antibodies against APP metabolites.
- Analysis of neuronal survival rates under various treatment conditions.
- Conditioning medium experiments to assess secreted APP's role.
Main Results:
- Antibodies targeting A beta (4G8, 6E10, R3659) enhanced neuronal survival by 30%.
- Antibodies against the APP N-terminus (22C11) reduced neuronal survival by 53%.
- Conditioned medium from neurons attenuated apoptosis, an effect abolished by APP-soluble (APPs) removal.
Conclusions:
- APP cleavage products differentially regulate neuronal survival via an autocrine loop.
- These findings support a model of Alzheimer's disease involving altered APP metabolism.