Where Kinesins and Human Health Meet
Cancer
Research and clinical trials are attempting to unlock the potential of mitotic kinesin as treatment for cancer. Current tubulin-inhibiting drugs have been quite successful in disrupting mitosis and thus preventing cancerous cell proliferation. However, as tubulin plays essential cellular roles outside of mitosis, these drugs become toxic at low levels, limiting their use as a practical cancer treatment.
Following the same logic of halting cancerous cell proliferation by disrupting mitosis, many are looking to the potential of mitotic kinesins. As mitotic kinesins’ functions are limited to mitosis they may offer a more advantageous branch of anti-mitotic drugs without the low level toxicity.
View links to clinical trials at the US National Institutes of Health web site.
View links to clinical trials at the American Association for Cancer Research web site.
Neuronal Function
Several kinesins are involved in neuronal transport and mutants of these kinesins in Drosophila show impaired neuronal function. Hypothetically, defects/mutations in kinesin-encoding genes may explain many of the various neurological abnormalities seen in humans. In fact, the most common neurological disorder, affecting 1 in every 2.500 to 10,000 people, Charcot Marie Tooth Disease Type II, has already been linked to a mutation in Kif1B known as Kif1Bbeta. In addition, a mutation in Trak1, a kinesin-binding protein, has been linked to hypertonia (an abnormal increase in muscle tension due to defective neural pathways, characteristic of many neurological disorders).
View more information on Kif1B on the NCBI web site.
View paper (Zhao et al 2001 Cell 105 587) linking Kif1Bbeta to Charcot Maire Tooth Disease.
View paper (Gilbert et al 2005 Nature Genetics 38 245) linking Trak1 to hypertonia.
View recent articles on kinesins’ roles in neurological function on the PUBMED database.
General Health
Playing such a vital cellular role, defective/mutant kinesins seem would easily hinder human health. Currently, defective kinesins are being studied as the possible causes of infertility, spontaneous abortion, neonatal chromosome disorders, aneuploidy, neoplasia, and various developmental disorders.
Specifically, in mice, a mutation in Kif3B has been linked to the randomization of left-right asymmetry. Mutations in Kif3B result in the formation of defectively functioning cilia or cease the cilia’s formation altogether. As these cilia are responsible for the proper left-right asymmetrical development of the heart and other organs during embryogenesis, the Kif3B mutations can have costly consequences.
In light of this dependence of cilia upon kinesin, kinsein mutations are also being looked at as the possible cause of various other intraflagellar transport and cilia-dependent diseases including; polycycstic kidney disease (PKD) and primary ciliary dyskinesia (PCD) diseases such as Kartagener’s Syndrome.
View paper (Nonaka et al 1998 Cell 95 829) linking Kif3B to left-right asymmetry.
View paper (Lin et al 2003 PNAS 100 9) linking Kif3B to polycystic kidney disease.
Find more information on PKD on the NCBI web site.
Find more information on PCD at the PCD Foundation web site or at the UNC PCD web site.
View recent articles on kinesin-related disorders on the PUBMED database.
Links to Health Agencies:
March of Dimes
Birth Defects Foundation
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Created 7 July 1996 20:00 GMT
Modified 25 June 2008 18:40 GMT
