TGF-β1 protects against Aβ-neurotoxicity via the phosphatidylinositol-3-kinase pathway
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beta-Amyloid (A beta) injection into the rat dorsal hippocampus had a small neurotoxic effect that was amplified by i.c.v. injection of SB431542, a selective inhibitor of transforming growth factor-beta (TGF-beta) receptor. This suggested that TGF-beta acts as a factor limiting A beta toxicity. We examined the neuroprotective activity of TGF-beta1 in pure cultures of rat cortical neurons challenged with A beta. Neuronal death triggered by A beta is known to proceed along an aberrant re-activation of the cell cycle, and involves late beta-catenin degradation and tau hyperphosphorylation. TGF-beta1 was equally protective when added either in combination with, or 6 h after A beta. Co-added TGF-beta1 prevented A beta-induced cell cycle reactivation, whereas lately added TGF-beta1 had no effect on the cell cycle, but rescued the late beta-catenin degradation and tau hyperphosphorylation. The phosphatidylinositol-3-kinase (PI-3-K) inhibitor, LY294402, abrogated all effects. Thus, TGF-beta1 blocks the whole cascade of events leading to A beta neurotoxicity by activating the PI-3-K pathway.
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Pathways neuroprotective in Alzheimer's disease appeared more cohesive in AD resistant neurons than in vulnerable neurons, namely the transforming growth factor beta receptor signaling pathway (in DG) and the canonical Wnt signaling pathway (in DG, S1 and V1).
“We found that pathways neuroprotective in AD (Caraci et al., 2008; Liu et al., 2014; Tesseur et al., 2006)appeared more cohesive in AD resistant neurons than in vulnerable neurons, namely the transforming growth factor beta receptor signaling pathway (in DG) and the canonical Wnt signaling pathway (in DG, S1 and V1).”
From Selective Neuronal Vulnerability in Alzheimer’s Disease: A Network-Based Analysis (2020) · cites this paper as Caraci et al., 2008
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- Authors
- Caraci, F., Battaglia, G., Busceti, C., Biagioni, F., Mastroiacovo, F., Bosco, P., Drago, F., Nicoletti, F., Sortino, M. A., & Copani, A.
- Affiliations
- University of Catania (IT)
- Istituto Neurologico Mediterraneo (IT)
- Oasi Maria SS (IT)
- Corresponding author
- Caraci, Filippo
- ORCID
- Venue
- Neurobiology of Disease
- Publisher
- Elsevier BV
- Published
- 2008-05
- Volume
- 30
- Issue
- 2
- Pages
- 234-242
- ISSN
- 0969-9961 (ISSN-L)
- OpenAlex
- W2038304336
- Cited by
- 79
- References
- 58
- Citations by year
- 2025: 4 · 2024: 4 · 2022: 3 · 2021: 6 · 2020: 5 · 2019: 2 · 2018: 3 · 2017: 4 · 2016: 9 · 2015: 9 · 2014: 6 · 2013: 5 · 2012: 5
- FWCI
- 3.17
- Type
- journal article
- Language
- en
- Open access
- green
- doaj.org
- Licence
- Locations
- Neurobiology of Disease (publishedVersion)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
- Funders
- Ministero dell'Università e della Ricerca
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Keywords
- TGF-β1, amyloid-beta toxicity, phosphatidylinositol 3-kinase pathway, neuroprotection, β-catenin degradation, tau hyperphosphorylation, cell cycle re-entry, cortical neurons, Alzheimer's disease, SB431542
- MeSH terms
- Phosphoinositide-3 Kinase Inhibitors, Animals, Cells, Cultured, Chromones, Male, Morpholines, Neurons, Signal Transduction, Amyloid beta-Peptides, Rats, Wistar, Neuroprotective Agents, Phosphatidylinositol 3-Kinases, Rats, Transforming Growth Factor beta1
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