Amyloid peptide toxicity and microtubule-stabilizing drugs

M. L. Michaelis, Y. Chen, S. Hill, E. Reiff, G. Georg, A. Rice, K. Audus

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

Based on microtubule (MT) disruption observed in primary neurons exposed to fibrillar amyloid peptides (Aβ), we tested the potential protective effect of MT-stabilizing drugs such as Taxol® against Aβ-induced disruption of the cytoskeleton. Although Taxol® was strongly protective, the fact that it does not cross the blood brain barrier (BBB) led us to synthesize and test other agents with MT-stabilizing properties and possible penetration into the brain. Our studies have thus far demonstrated that several MT-stabilizing agents, including some with structures quite different from that of Taxol®, showed significant protective effects. However, not all agents that promoted MT-assembly were protective, suggesting additional mechanisms are involved in the actions of the drugs. A small number of neuroprotective compounds appear to have potential to enter the brain and thus might be tested to see if they slow progression of neurodegeneration in an appropriate animal model of Alzheimer's disease.

Original languageEnglish (US)
Pages (from-to)101-105
Number of pages5
JournalJournal of Molecular Neuroscience
Volume19
Issue number1-2
DOIs
StatePublished - Jan 1 2002

Keywords

  • Aβ toxicity
  • Blood brain barrier
  • Microtubule-stabilizing drugs
  • Neurofibrillary pathology
  • Primary neurons

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