Michaelis M L [a]. Ranciat N. Chen Y. Bechtel M. Ragan R. Hepperle M.
Liu Y. Georg G.
Protection against beta-amyloid toxicity in primary neurons by paclitaxel (Taxol), Journal of Neurochemistry 70(4) :1623-1627, 1998.
Abstract
Neurofibrillary tangles in Alzheimer's disease contain aggregates of
abnormally phosphorylated microtubule-associated protein tau, indicating that
microtubule breakdown is a primary event in the neurodegenerative cascade.
Recent studies have shown that addition to neuronal cultures of
amyloid peptides found in Alzheimer's leads to abnormal
phosphorylation of tau and neurofibrillary pathology. We tested the
possibility that the microtubule-stabilizing drug paclitaxel (Taxol) might
protect primary neurons against amyloid-induced
toxicity. Neurons exposed to aggregated
amyloid peptides 25-35 and 1-42 became pyknotic with
degenerating neurites within 24 h. Treatment of cultures with paclitaxel
either 2 h before or 2 h after addition of the peptide prevented these
morphological alterations. When numbers of viable cells were determined in
cultures exposed to amyloid peptide with or without
paclitaxel for 24 or 96 h, the percentage of surviving cells was
significantly higher in paclitaxel-treated cultures, and activation of the
apoptosis-associated protease CPP32 was significantly reduced. These
observations indicate that microtubule-stabilizing drugs may help slow
development of the neurofibrillary pathology that leads to the loss of
neuronal integrity in Alzheimer's disease.
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