title: Altered microtubule dynamics in neurodegenerative disease: Therapeutic potential of microtubule-stabilizing drugs.
abstract: Many neurodegenerative diseases are characterized by deficiencies in neuronal axonal transport, a process in which cellular cargo is shuttled with the aid of molecular motors from the cell body to axonal termini and back along microtubules (MTs). Proper axonal transport is critical to the normal functioning of neurons, and impairments in this process could contribute to the neuronal damage and death that is characteristic of neurodegenerative disease. Although the causes of axonal transport abnormalities may vary among the various neurodegenerative conditions, in many cases it appears that the transport deficiencies result from a diminution of axonal MT stability. Here we review the evidence of MT abnormalities in a number of neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis and traumatic brain injury, and highlight the potential benefit of MT-stabilizing agents in improving axonal transport and nerve function in these diseases. Moreover, we discuss the challenges associated with the utilization of MT-stabilizing drugs as therapeutic candidates for neurodegenerative conditions.
authors.affiliation: Center for Neurodegenerative Disease Research, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, United States. Electronic address: kbrunden@upenn.edu.
authors.forename: Kurt R
authors.initials: KR
authors.lastname: Brunden
authors.affiliation: Center for Neurodegenerative Disease Research, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, United States.
authors.forename: Virginia M-Y
authors.initials: VM
authors.lastname: Lee
authors.affiliation: Department of Chemistry, School of Arts and Science, University of Pennsylvania, Philadelphia, PA 19104, United States.
authors.forename: Amos B
authors.initials: AB
authors.lastname: Smith
authors.affiliation: Center for Neurodegenerative Disease Research, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, United States.
authors.forename: John Q
authors.initials: JQ
authors.lastname: Trojanowski
authors.affiliation: Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA 92093, United States.
authors.forename: Carlo
authors.initials: C
authors.lastname: Ballatore
mesh_terms: D000818:Animals; D006801:Humans; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism*; D019636:Neurodegenerative Diseases / Q000188:drug therapy* / Q000378:metabolism*; D050257:Tubulin Modulators / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D050257:Tubulin Modulators
keywords: Alzheimer; Amyotrophic lateral sclerosis; Axons; Frontotemporal lobar degeneration; Microtubules; Neurodegeneration; Parkinson; Transport; Traumatic brain injury