05-14-2014, 06:25 PM
A new study suggests that novel protein fragments (peptides) can protect against Alzheimer’s disease pathology, including the Alzheimer's disease (AD) toxin (amyloid-β 1–42 peptide) and also against tau-like protein tangle formation and cognitive decline in a mouse model of AD. The study, published in the Journal of Alzheimer's Disease, comes from researchers in Tel Aviv University in Israel.
Alzheimer’s disease is a devastating neurodegenerative condition characterised by amyloid-β 1–42 peptide accumulation and tangles formed from abnormal tau proteins, a marker of cognitive decline. Research is focused on trying to elucidate the pathology as well as harness potential protective or regenerative brain cell properties that could contribute to therapy. AD and other neurodegenerative diseases feature breakdown of the microtubule network. This forms part of all cells in our bodies. In nerve cells it is particularly important for transport of essential proteins and communication between cells. The research in the current study focused on the microtubules, in particular on the microtubule subunit tubulin and in the microtubule associated protein, tau.
Previously, the researchers in this project had identified a peptide called NAP, which acts to stabilise microtubules and is a drug candidate showing promise in treatment of mild cognitive impairment. In the current study, the research team scanned the protein sequences of tubulin and tau and identified NAP-like homologies. They derived NAP-like peptides called NAT and STPTAIPQ from tubulin, and TAP from tau. These peptides were shown to provide neuroprotection against the Alzheimer's disease (AD) toxin, the amyloid-β 1–42 peptide, in a tissue culture in vitro model. TAP and NAT were more potent than STPTAIPQ . Lead author Prof Ilana Gozes explains: “The newly discovered protein fragments, just like NAP before them, work to protect microtubules, thereby protecting the cell."
In an in vivo mouse model of AD at 10 months old, both NAT and TAP were able to inhibit the tau-like aggregation that characterises cognitive decline in AD. Further testing of NAT showed that in the AD mouse model, in which there was significantly decreased levels of NAP parent protein, NAT was able to restore NAP levels. Brain-to-body mass ratio, which is an indicator of brain degeneration, was also significantly decreased in the AD mouse model compared to normal mice, but was also restored to normal by NAT treatment. Dr Gozes explains: "We clearly see here the protective effect of the treatment…We witnessed the restorative and protective effects of totally new protein fragments, derived from proteins critical to cell function, in tissue cultures and on animal models."
Sources
Gozes, I., Iram, T., Maryanovsky, E., Arviv, C., Rozenberg, L., Schirer, Y., Giladi, E. and Furman-Assaf, S. (2014). Novel Tubulin and Tau Neuroprotective Fragments Sharing Structural Similarities with the Drug Candidate NAP (Davuentide). Journal of Alzheimer's Disease, DOI 10.3233/JAD-131664
Press release: Tel Aviv University, available at http://www.aftau.org/newsroom?7d56804a-2...cacd9b1135
Alzheimer’s disease is a devastating neurodegenerative condition characterised by amyloid-β 1–42 peptide accumulation and tangles formed from abnormal tau proteins, a marker of cognitive decline. Research is focused on trying to elucidate the pathology as well as harness potential protective or regenerative brain cell properties that could contribute to therapy. AD and other neurodegenerative diseases feature breakdown of the microtubule network. This forms part of all cells in our bodies. In nerve cells it is particularly important for transport of essential proteins and communication between cells. The research in the current study focused on the microtubules, in particular on the microtubule subunit tubulin and in the microtubule associated protein, tau.
Previously, the researchers in this project had identified a peptide called NAP, which acts to stabilise microtubules and is a drug candidate showing promise in treatment of mild cognitive impairment. In the current study, the research team scanned the protein sequences of tubulin and tau and identified NAP-like homologies. They derived NAP-like peptides called NAT and STPTAIPQ from tubulin, and TAP from tau. These peptides were shown to provide neuroprotection against the Alzheimer's disease (AD) toxin, the amyloid-β 1–42 peptide, in a tissue culture in vitro model. TAP and NAT were more potent than STPTAIPQ . Lead author Prof Ilana Gozes explains: “The newly discovered protein fragments, just like NAP before them, work to protect microtubules, thereby protecting the cell."
In an in vivo mouse model of AD at 10 months old, both NAT and TAP were able to inhibit the tau-like aggregation that characterises cognitive decline in AD. Further testing of NAT showed that in the AD mouse model, in which there was significantly decreased levels of NAP parent protein, NAT was able to restore NAP levels. Brain-to-body mass ratio, which is an indicator of brain degeneration, was also significantly decreased in the AD mouse model compared to normal mice, but was also restored to normal by NAT treatment. Dr Gozes explains: "We clearly see here the protective effect of the treatment…We witnessed the restorative and protective effects of totally new protein fragments, derived from proteins critical to cell function, in tissue cultures and on animal models."
Sources
Gozes, I., Iram, T., Maryanovsky, E., Arviv, C., Rozenberg, L., Schirer, Y., Giladi, E. and Furman-Assaf, S. (2014). Novel Tubulin and Tau Neuroprotective Fragments Sharing Structural Similarities with the Drug Candidate NAP (Davuentide). Journal of Alzheimer's Disease, DOI 10.3233/JAD-131664
Press release: Tel Aviv University, available at http://www.aftau.org/newsroom?7d56804a-2...cacd9b1135
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