title: Apoptosis inhibition can be threatening in Aβ-induced neuroinflammation, through promoting cell proliferation.
abstract: Neuronal apoptosis in neurodegenerative diseases is correlated with inflammatory reactions. The beneficial or detrimental role of apoptosis in neuroinflammation is unclear. In this study, we injected β-amyloid peptide into the rat cortex for induction of neuroinflammation in hippocampus. We observed an increase in TNF-α as an inflammatory cytokine and caspase3 and TUNEL-positive cells as apoptotic marker. As far as ability of TNF-α to induce apoptosis or activate NF-kβ, the question is what will happen if the balance between two pathways is disturbed by inhibition of apoptosis. Using caspase inhibitors, we inhibited apoptosis and assessed NF-kβ, Hsp 70 (a hallmark of cancer), cmyc (proto-oncogene) and p53 (tumor suppressor protein). There was an unexpected decrease in NF-kβ while Hsp70 and cmyc upregulated and p53 decreased. These results imply that inhibition of apoptosis due to increased susceptibility to abnormal mitosis may not provide a reliable strategy for treatment of neuroinflammatory diseases.
authors.affiliation: Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Evin, PO Box 19839-63113, Tehran, Iran.
authors.forename: A
authors.initials: A
authors.lastname: Abdi
authors.forename: H
authors.initials: H
authors.lastname: Sadraie
authors.forename: L
authors.initials: L
authors.lastname: Dargahi
authors.forename: L
authors.initials: L
authors.lastname: Khalaj
authors.forename: A
authors.initials: A
authors.lastname: Ahmadiani
mesh_terms: D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D015415:Biomarkers / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D061945:Caspase Inhibitors; D049109:Cell Proliferation / Q000187:drug effects*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D004660:Encephalitis / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology*; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology; D006801:Humans; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers; D061945:Caspase Inhibitors; D015853:Cysteine Proteinase Inhibitors; D018840:HSP70 Heat-Shock Proteins; C000715470:MAS1 protein, human; D016328:NF-kappa B; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc; D014409:Tumor Necrosis Factor-alpha; D053148:Caspase 3