Affiliation:
1. Department of Neurobiology, University of Osnabrück, Osnabrück, Germany
Abstract
:
The microtubule skeleton plays an essential role in nerve cells as the most important
structural determinant of morphology and as a highway for axonal transport processes. Many
neurodegenerative diseases are characterized by changes in the structure and organization of
microtubules and microtubule-regulating proteins such as the microtubule-associated protein
tau, which exhibits characteristic changes in a whole class of diseases collectively referred to
as tauopathies. Changes in the dynamics of microtubules appear to occur early under
neurodegenerative conditions and are also likely to contribute to age-related dysfunction of
neurons. Thus, modulating microtubule dynamics and correcting impaired microtubule
stability can be a useful neuroprotective strategy to counteract disruption of the microtubule
system in disease and aging. In this article, we review current microtubule-directed
approaches for the treatment of neurodegenerative diseases with microtubules as drug target,
tau as drug target, and posttranslational modifications as potential modifiers of the
microtubule system. We discuss limitations of the approaches that can be traced back to the
rather unspecific mechanism of action, which causes undesirable side effects on non-neuronal
cell types or which are due to the disruption of non-microtubule-related interactions. We also
develop some thoughts on how the specificity of the approaches can be improved and what
further targets could be used for modulating substances.
Publisher
Bentham Science Publishers Ltd.
Subject
Pharmacology (medical),Psychiatry and Mental health,Neurology (clinical),Neurology,Pharmacology,General Medicine
Cited by
11 articles.
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