Microtubule dysfunction: A common feature of neurodegenerative diseases: International Journal of Molecular Sciences

A. Sferra, F. Nicita, E. Bertini

Research output: Contribution to journalArticlepeer-review

Abstract

Neurons are particularly susceptible to microtubule (MT) defects and deregulation of the MT cytoskeleton is considered to be a common insult during the pathogenesis of neurodegenerative disorders. Evidence that dysfunctions in the MT system have a direct role in neurodegeneration comes from findings that several forms of neurodegenerative diseases are associated with changes in genes encoding tubulins, the structural units of MTs, MT-associated proteins (MAPs), or additional factors such as MT modifying enzymes which modulating tubulin post-translational modifications (PTMs) regulate MT functions and dynamics. Efforts to use MT-targeting therapeutic agents for the treatment of neurodegenerative diseases are underway. Many of these agents have provided several benefits when tested on both in vitro and in vivo neurodegenerative model systems. Currently, the most frequently addressed therapeutic interventions include drugs that modulate MT stability or that target tubulin PTMs, such as tubulin acetylation. The purpose of this review is to provide an update on the relevance of MT dysfunctions to the process of neurodegeneration and briefly discuss advances in the use of MT-targeting drugs for the treatment of neurodegenerative disorders. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.
Original languageEnglish
Pages (from-to)1-36
Number of pages36
JournalInt. J. Mol. Sci.
Volume21
Issue number19
DOIs
Publication statusPublished - 2020

Keywords

  • Microtubule dysfunctions
  • Microtubule-targeting compounds
  • Microtubules
  • Neurodegeneration
  • alpha tubulin
  • brain derived neurotrophic factor
  • central nervous system agents
  • glutamic acid
  • histone deacetylase 6
  • parkin
  • tau protein
  • tubulin
  • tyrosine
  • microtubule associated protein
  • brain tissue
  • cell body
  • cell membrane
  • centrosome
  • chromatin
  • degenerative disease
  • dendrite
  • dopaminergic nerve cell
  • drug targeting
  • gene mutation
  • histone code
  • human
  • in vitro study
  • microtubule
  • mutation
  • nerve cell
  • nerve degeneration
  • neurite outgrowth
  • nonhuman
  • pathogenesis
  • point mutation
  • protein acetylation
  • protein phosphorylation
  • protein protein interaction
  • Review
  • acetylation
  • cytoskeleton
  • genetics
  • metabolism
  • pathology
  • protein processing
  • Acetylation
  • Cytoskeleton
  • Humans
  • Microtubule-Associated Proteins
  • Neurodegenerative Diseases
  • Neurons
  • Protein Processing, Post-Translational
  • tau Proteins
  • Tubulin

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