Apoptosis inhibition can be threatening in Aβ-induced neuroinflammation, through promoting cell proliferation.
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.
Abdi
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A
Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Evin, PO Box 19839-63113, Tehran, Iran.
Sadraie
H
H
Dargahi
L
L
Khalaj
L
L
Ahmadiani
A
A
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
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