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

Maddalena Napolitano, Loredana Costa, Roberto Piacentini, Claudio Grassi, Antonio Lanzone, Alberto Gulino

Research output: Contribution to journalArticlepeer-review

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 A. β-amyloid-induced toxicity is typically associated with apoptosis. Here, we investigated the effect of 17. β-estradiol (E2) on A. β-induced toxicity in cerebellar granule cells (CGCs). Our data showed a significant induction of apoptosis in neurons treated with A. β, and the addition of E2 reduced this effect. In addition, E2 reduced the A. β-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 A. β-induced apoptosis in neuronal cells by preventing mitochondrial dysfunction and interfering with the JNK signalling cascade.

Original languageEnglish
Pages (from-to)134-139
Number of pages6
JournalNeuroscience Letters
Volume561
DOIs
Publication statusPublished - Feb 21 2014

Keywords

  • Aβ-Amyloid
  • Alzheimer's disease
  • Bcl-2 family
  • Estradiol
  • JNK
  • Mitochondria

ASJC Scopus subject areas

  • Neuroscience(all)

Fingerprint

Dive into the research topics of '17β-Estradiol protects cerebellar granule cells against β-amyloid-induced toxicity via the apoptotic mitochondrial pathway'. Together they form a unique fingerprint.

Cite this