Inhibition of the neuronal NFκB pathway attenuates bortezomib-induced neuropathy in a mouse model
Alé, Albert (Universitat Autònoma de Barcelona. Institut de Neurociències)
Bruna, Jordi (Universitat Autònoma de Barcelona. Institut de Neurociències)
Calls, Aina (Universitat Autònoma de Barcelona. Institut de Neurociències)
Karamita, Maria (Hellenic Pasteur Institute)
Haralambous, Sylva (Hellenic Pasteur Institute)
Probert, Lesley (Hellenic Pasteur Institute)
Navarro, X. (Xavier) (Universitat Autònoma de Barcelona. Institut de Neurociències)
Udina i Bonet, Esther (Universitat Autònoma de Barcelona. Institut de Neurociències)

Fecha:	2016
Resumen:	© 2016 Elsevier B. V. Bortezomib is a proteasome inhibitor with a remarkable antitumor activity, used in the clinic as first line treatment for multiple myeloma. One hallmark of bortezomib mechanism of action in neoplastic cells is the inhibition of nuclear factor kappa B (NFκB), a transcription factor involved in cell survival and proliferation. Bortezomib-induced peripheral neuropathy is a dose-limiting toxicity that often requires adjustment of treatment and affects patient's prognosis and quality of life. Since disruption of NFκB pathway can also affect neuronal survival, we assessed the role of NFκB in bortezomib-induced neuropathy by using a transgenic mouse that selectively provides blockage of the NFκB pathway in neurons. Interestingly, we observed that animals with impaired NFκB activation developed significantly less severe neuropathy than wild type animals, with particular preservation of large myelinated fibers, thus suggesting that neuronal NFκB activation plays a positive role in bortezomib induced neuropathy and that bortezomib treatment might induce neuropathy by inhibiting NFκΒ in non-neuronal cell types or by targeting other signaling pathways. Therefore, inhibition of NFκB might be a promising strategy for the cotreatment of cancer and neuropathy.
Ayudas:	Instituto de Salud Carlos III PI1501303
Derechos:	Aquest material està protegit per drets d'autor i/o drets afins. Podeu utilitzar aquest material en funció del que permet la legislació de drets d'autor i drets afins d'aplicació al vostre cas. Per a d'altres usos heu d'obtenir permís del(s) titular(s) de drets.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió sotmesa a revisió
Materia:	Bortezomib ; Neurotoxicity ; Nuclear factor kappa b ; Peripheral neuropathy ; Proteasome inhibition ; Sensory neurons ; SDG 3 - Good Health and Well-being
Publicado en:	NeuroToxicology, Vol. 55 (2016) , p. 58-64, ISSN 1872-9711

DOI: 10.1016/j.neuro.2016.05.004

21 p, 1.0 MB

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Documentos de investigación > Documentos de los grupos de investigación de la UAB > Centros y grupos de investigación (producción científica) > Ciencias de la salud y biociencias > Institut de Neurociències (INc)
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