Alzheimer's disease (AD) is a well-studied neurodegenerative disorder; nevertheless, significant therapeutic agents for the pharmacological treatment of this neuropathology are unavailable to date. The toxicity of amyloid β-peptide (Aβ) has been implicated as a critical cause in the development of AD, and Aβ-amyloid-induced toxicity is typically associated with apoptosis. Here, we investigated the effect of 17β-estradiol (E2) on Aβ-induced toxicity in cerebellar granule cells (CGCs). Our data showed a significant induction of apoptosis in neurons treated with Aβ, and the addition of E2 reduced this effect. In addition, E2 reduced the Aβ-induced up-regulation of Bax and down-regulation of Bcl-xL, and inhibited the subsequent mitochondrial release of cytochrome c and activation of caspase-3. Moreover, E2 inhibited Aβ-induced c-Jun N-terminal protein kinase (JNK) activation. Taken together, these findings indicate that E2 protects against Aβ-induced apoptosis in neuronal cells by preventing mitochondrial dysfunction and interfering with the JNK signalling cascade.

Napolitano, M., Costa, L., Piacentini, R., Grassi, C., Lanzone, A., Gulino, R. A., 17β-estradiol protects cerebellar granule cells against β-amyloid-induced toxicity via the apoptotic mitochondrial pathway, <<NEUROSCIENCE LETTERS>>, 2014; 561 (Febbraio): 134-139. [doi:10.1016/j.neulet.2013.11.030] [http://hdl.handle.net/10807/55511]

17β-estradiol protects cerebellar granule cells against β-amyloid-induced toxicity via the apoptotic mitochondrial pathway

Napolitano, Monica;Costa, Luigi;Piacentini, Roberto;Grassi, Claudio;Lanzone, Antonio;Gulino, Rosario Alfio
2014

Abstract

Alzheimer's disease (AD) is a well-studied neurodegenerative disorder; nevertheless, significant therapeutic agents for the pharmacological treatment of this neuropathology are unavailable to date. The toxicity of amyloid β-peptide (Aβ) has been implicated as a critical cause in the development of AD, and Aβ-amyloid-induced toxicity is typically associated with apoptosis. Here, we investigated the effect of 17β-estradiol (E2) on Aβ-induced toxicity in cerebellar granule cells (CGCs). Our data showed a significant induction of apoptosis in neurons treated with Aβ, and the addition of E2 reduced this effect. In addition, E2 reduced the Aβ-induced up-regulation of Bax and down-regulation of Bcl-xL, and inhibited the subsequent mitochondrial release of cytochrome c and activation of caspase-3. Moreover, E2 inhibited Aβ-induced c-Jun N-terminal protein kinase (JNK) activation. Taken together, these findings indicate that E2 protects against Aβ-induced apoptosis in neuronal cells by preventing mitochondrial dysfunction and interfering with the JNK signalling cascade.
Inglese
Napolitano, M., Costa, L., Piacentini, R., Grassi, C., Lanzone, A., Gulino, R. A., 17β-estradiol protects cerebellar granule cells against β-amyloid-induced toxicity via the apoptotic mitochondrial pathway, <>, 2014; 561 (Febbraio): 134-139. [doi:10.1016/j.neulet.2013.11.030] [http://hdl.handle.net/10807/55511]
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/10807/55511
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