Oxidative stress, DNA damage, and c-Abl signaling: At the crossroad in neurodegenerative diseases?
Open accessAbstract
The c-Abl tyrosine kinase is implicated in diverse cellular activities including growth factor signaling, cell adhesion, oxidative stress, and DNA damage response. Studies in mouse models have shown that the kinases of the c-Abl family play a role in the development of the central nervous system. Recent reports show that aberrant c-Abl activation causes neuroinflammation and neuronal loss in the forebrain of transgenic adult mice. In line with these observations, an increased c-Abl activation is reported in human neurodegenerative pathologies, such as Parkinson's, and Alzheimer's diseases. This suggests that aberrant nonspecific posttranslational modifications induced by c-Abl may contribute to fuel the recurrent phenotypes/features linked to neurodegenerative disorders, such as an impaired mitochondrial function, oxidative stress, and accumulation of protein aggregates. Herein, we review some reports on c-Abl function in neuronal cells and we propose that modulation of different aspects of c-Abl signaling may contribute to mediate the molecular events at the interface between stress signaling, metabolic regulation, and DNA damage. Finally, we propose that this may have an impact in the development of new therapeutic strategies.
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Alterations in c-Abl activity play a central role in several neurodegenerative diseases, including PD and AD.
“Indeed, emerging evidence shows that alterations in c-Abl ac tivity play a central role in several neurodegenerative diseases, including PD and AD (Gonfloni et al., 2012; Hebron et al., 2013a; Imam et al., 2011; Jing et al., 2009; Karuppagounder et al., 2014; Ko et al., 2010; Lindholm et al., 2016; Schlatterer et al., 2011).”
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“neurodegenerative diseases, including PD and AD (Gonfloni et al., 2012; Hebron et al., 2013a; Imam et al., 2011; Jing et al., 2009; Karuppagounder et al., 2014; Ko et al., 2010; Lindholm et al., 2016; Schlatterer et al., 2011).”
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- Authors
- Gonfloni, S., Maiani, E., Di Bartolomeo, C., Diederich, M., & Cesareni, G.
- Affiliations
- University of Rome Tor Vergata (IT)
- Department of Biology, University of Rome “Tor Vergata,” Via della Ricerca Scientifica, 00133 Rome, Italy
- Hôpital Kirchberg (LU)
- Corresponding author
- Gonfloni, Stefania
- Venue
- International Journal of Cell Biology
- Publisher
- Wiley
- Published
- 2012
- Volume
- 2012
- Pages
- 1-7
- ISSN
- 1687-8876 (ISSN-L)
- 1687-8884
- PMC
- PMC3385657
- OpenAlex
- W2108576954
- Cited by
- 63
- References
- 60
- Citations by year
- 2026: 2 · 2025: 7 · 2024: 4 · 2023: 7 · 2022: 8 · 2021: 4 · 2020: 2 · 2019: 2 · 2018: 2 · 2017: 7 · 2016: 3 · 2015: 2 · 2014: 8 · 2013: 5
- FWCI
- 3.22
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- International Journal of Cell Biology (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Cineca Institutional Research Information System (Tor Vergata University) (submittedVersion, cc-by-nc-nd)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- AIRC
- Recherche Cancer et Sang Association
- Recherches Scientifiques Luxembourg Association
- “Action Lions Vaincre le Cancer’’ Association
- Televie Luxembourg
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Keywords
- c-Abl kinase, oxidative stress, DNA damage response, neurodegenerative diseases, Parkinson's disease, Alzheimer's disease, neuroinflammation, neuronal loss, post-translational modification, mitochondrial dysfunction, protein aggregation, treatment options
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