title: 17β-estradiol protects cerebellar granule cells against β-amyloid-induced toxicity via the apoptotic mitochondrial pathway.
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.
authors.affiliation: Department of Molecular Medicine, University "La Sapienza" Rome, Italy. Electronic address: maddalena.napolitano@uniroma1.it.
authors.forename: Maddalena
authors.initials: M
authors.lastname: Napolitano
authors.affiliation: Department of Molecular Medicine, University "La Sapienza" Rome, Italy.
authors.forename: Loredana
authors.initials: L
authors.lastname: Costa
authors.affiliation: Institute of Human Physiology, Catholic University, Rome, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Piacentini
authors.affiliation: Institute of Human Physiology, Catholic University, Rome, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Grassi
authors.affiliation: Institute of Obstetrics and Gynaecology, Catholic University, Rome, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Lanzone
authors.affiliation: Department of Molecular Medicine, University "La Sapienza" Rome, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Gulino
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism* / Q000633:toxicity; D000818:Animals; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D002525:Cerebellar Cortex / Q000166:cytology*; D045304:Cytochromes c / Q000378:metabolism; D004789:Enzyme Activation; D004958:Estradiol / Q000494:pharmacology*; D004967:Estrogens / Q000494:pharmacology*; D005786:Gene Expression Regulation; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010446:Peptide Fragments / Q000378:metabolism* / Q000633:toxicity; D017208:Rats, Wistar; D015398:Signal Transduction; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D051020:bcl-X Protein / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; C494812:Bcl2l1 protein, mouse; D004967:Estrogens; D018696:Neuroprotective Agents; D010446:Peptide Fragments; C074636:amyloid beta-protein (25-35); D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; D004958:Estradiol; D045304:Cytochromes c; D048670:MAP Kinase Kinase 4; D053148:Caspase 3
keywords: Alzheimer's disease; Aβ-Amyloid; Bcl-2 family; Estradiol; JNK; Mitochondria