| Alzheimer's disease (AD) is a major health problem and expense for the United States. Unfortunately, there is no pharmacological treatment currently available that can cure, reverse, or even slow down this devastating neurodegenerative disorder. The deposition of β-amyloid peptide (Aβ), the hyperphosphorylation of τ protein and the death of neurons in certain brain regions are characteristic features of AD. The studies presented in this dissertation demonstrate that both naturally occurring and synthetic, structurally diverse microtubule (MT)-stabilizing compounds, e.g., paclitaxel, Taxotere®, Epothilone, UK100, and GS164 can markedly protect neurons against Aβ-induced morphological degeneration, significantly increase cell survival, and substantially block Aβ-induced MT network disruption in an in vitro tissue culture AD model. These observations suggest that MT stabilization is a critical and central component of the neuroprotective actions afforded by these agents. Moreover, these results suggest that agents that enhance MT-stability might provide dramatic protection against the degenerative cascade normally triggered by toxic Aβ that accumulates in the brains of AD patients. These results raise the possibility of using MT-stabilizing drugs as a novel therapeutic approach for the treatment of AD. |
