Integrated Nanostructured Systems

Axonal transport and neurodegenerative disease; Nanomedicine

Axonal transport in neurodegenerative disease

Within axons vital cargoes must be transported over great distances along microtubule tracks to maintain cell viability. In neuronal cells, many proteins function in sending and receiving messages, cell repair, and cell protection. Our interest is to elucidate if degeneration of neurons in two neurodegenerative diseases (Alzheimer’s disease or Huntington’s/other polyQ diseases), is related to a defect in this long distance transport system and what mechanisms facilitate the normal transport of APP and huntingtin.

Microtubule-based transport pathway as a therapeutic target

Our research is also focused on elucidating if MT-based transport pathways can be utilized to direct specific therapeutic aids to axonal blocks. In this regard, we are utilizing nanoparticles (NPs) since NPs can be conjugated with potential compounds or even siRNA. However, for NPs to be useful we first need to characterize NPs in the context of axonal transport. To explore this, we are using our robust in vivo movement assay and a compound that specifically suppressors blockages induced by pathogenic polyQ proteins. This work is been done in collaboration with Dr Jim Bergey and his team at the Institute of Lasers, Photonics and Biophotonics.

Stokin, G.B., Almenar-Queralt, A., Gunawardena S., Rodrigues, E.M., Lillo, C., Mount, S.L., Roberts, E.A., Williams, D.S., Goldstein, L.S.B. (2008) Presenilin-medated suppression of amyloid precursor protein-induced axonopathies. Hum Mol Genet: August 11.

Gunawardena, S. and Goldstein, L.S.B. (2005) Polyglutamine diseases and transport problems: Deadly traffic jams on neuronal highways. Archives of Neurology 62:46-51.

Gunawardena, S. and Goldstein, L.S.B. (2004) Cargo carrying motor vehicles on the neuronal highway: Transport pathways and neurodegenerative disease. Journal of Neurobiology 58:258-71.

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Gunawardena, S. and Rykowski, M.C. (2000). Direct evidence for interphase chromosome movement during the mid-blastula transition in Drosophila. Current Biology 10: 285-288.

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Gunawardena, S. and Rykowski, M. (1994). Looking at diploid interphase chromosomes. Methods in Cell Biology 44: 393-409.