Download Tau proteins which make up neurofibrillary tangles (NTs) are one

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Characterization of tau proteins during the development of human cortical neurons in culture
Presenter: Khin M. Win
Mentor: Dr. Jorge Busciglio
Neurofibrillary tangles (NFTs) made up of hyperphosphorylated tau are intraneuronal lesions present in
several neurodegenerative diseases including Alzheimer’s disease (AD). Although rodent species have been
used extensively to study NFT-related features, there are significant differences among tau isoforms
between humans and rodents. The aim of this research is to characterize the expression of tau isoforms in
cultured human cortical neurons grown on two different substrates: poly-L-lysine (PLL), a synthetic
molecule, and laminin (an extracellular matrix protein known to stimulate neuritic outgrowth and neuronal
maturation). The final goal is to establish an experimental model for future studies of molecular
mechanisms involving tau proteins in neurodegenerative diseases. Since tau, an axonal protein, plays a role
in early neuronal development, we monitored neurite outgrowth during the initial period of 4-5 days. We
performed immunostaining for measurement of neuritic lengths, and western blotting for characterization
of tau proteins and progressive expression of various tau isoforms. Our results indicate that laminin
stimulates longer neuritic processes than PLL, and that 3- and 4- repeat isoforms of human tau are
expressed in both PLL and laminin substrates. The similarities observed between human cortical neurons in
culture and mature neurons in the human brain suggest that this culture system will be a useful
experimental paradigm for molecular studies of tau pathology and development of NFT.