Apoptosis Inhibition Can Be Threatening in A beta-Induced Neuroinflammation, Through Promoting Cell Proliferation

作者：Abdi A; Sadraie H; Dargahi L; Khalaj L; Ahmadiani A^*

来源：Neurochemical Research, 2011, 36(1): 39-48.

DOI：10.1007/s11064-010-0259-3

• Neuroinflammation
• Apoptosis
• NF-kappa B
• Caspase-3
• 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 beta-amyloid peptide into the rat cortex for induction of neuroinflammation in hippocampus. We observed an increase in TNF-alpha as an inflammatory cytokine and caspase3 and TUNEL-positive cells as apoptotic marker. As far as ability of TNF-alpha to induce apoptosis or activate NF-k beta, 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-k beta, Hsp 70 (a hallmark of cancer), cmyc (proto-oncogene) and p53 (tumor suppressor protein). There was an unexpected decrease in NF-k beta 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.

• 出版日期2011-1