PreprintArticleVersion 1Preserved in Portico This version is not peer-reviewed
R406W Mutant Tau Protein Conjugated with GFP Aggregates in Cells and Phorbol 12-Myristate 13-Acetate Inhibits Mutant Tau Aggregation and Promotes Neurite Outgrowth in Human Cell Culture Model of Neurodegenerative Diseases
Version 1
: Received: 10 August 2023 / Approved: 10 August 2023 / Online: 11 August 2023 (09:00:28 CEST)
How to cite:
Tokunaga, Y.; Osugi, A.; Otsuyama, K.; Honda, T.; Hayashida, N. R406W Mutant Tau Protein Conjugated with GFP Aggregates in Cells and Phorbol 12-Myristate 13-Acetate Inhibits Mutant Tau Aggregation and Promotes Neurite Outgrowth in Human Cell Culture Model of Neurodegenerative Diseases. Preprints2023, 2023080889. https://doi.org/10.20944/preprints202308.0889.v1
Tokunaga, Y.; Osugi, A.; Otsuyama, K.; Honda, T.; Hayashida, N. R406W Mutant Tau Protein Conjugated with GFP Aggregates in Cells and Phorbol 12-Myristate 13-Acetate Inhibits Mutant Tau Aggregation and Promotes Neurite Outgrowth in Human Cell Culture Model of Neurodegenerative Diseases. Preprints 2023, 2023080889. https://doi.org/10.20944/preprints202308.0889.v1
Tokunaga, Y.; Osugi, A.; Otsuyama, K.; Honda, T.; Hayashida, N. R406W Mutant Tau Protein Conjugated with GFP Aggregates in Cells and Phorbol 12-Myristate 13-Acetate Inhibits Mutant Tau Aggregation and Promotes Neurite Outgrowth in Human Cell Culture Model of Neurodegenerative Diseases. Preprints2023, 2023080889. https://doi.org/10.20944/preprints202308.0889.v1
APA Style
Tokunaga, Y., Osugi, A., Otsuyama, K., Honda, T., & Hayashida, N. (2023). R406W Mutant Tau Protein Conjugated with GFP Aggregates in Cells and Phorbol 12-Myristate 13-Acetate Inhibits Mutant Tau Aggregation and Promotes Neurite Outgrowth in Human Cell Culture Model of Neurodegenerative Diseases. Preprints. https://doi.org/10.20944/preprints202308.0889.v1
Chicago/Turabian Style
Tokunaga, Y., Takeshi Honda and Naoki Hayashida. 2023 "R406W Mutant Tau Protein Conjugated with GFP Aggregates in Cells and Phorbol 12-Myristate 13-Acetate Inhibits Mutant Tau Aggregation and Promotes Neurite Outgrowth in Human Cell Culture Model of Neurodegenerative Diseases" Preprints. https://doi.org/10.20944/preprints202308.0889.v1
Abstract
Patients with neurodegenerative diseases (NDDs) are rapidly increasing all over the world. Alzheimer’s disease (AD), Parkinson’s disease, Huntington’s disease (HD), frontotemporal lobar degeneration (FTLD) and many other diseases are classified as NDDs, however, no therapeutic drugs have been developed against NDDs yet. As common phenomenon, protein oligomers and aggregates (inclusion bodies) are formed in neurons, and they trigger neuronal cell death and/or axonal degeneration. We have investigated the mechanisms of NDDs, and discovered several chemicals and peptides have potential to cure NDDs. Here, we show phorbol 12-myristate 13-acetate (PMA) significantly inhibits aggregate formation and promotes neurite regeneration in human neuronal cell culture model of NDDs, FTLD and AD. We expressed R406W mutant tau protein found in FTLD patients in human neuroblastoma SH-SY5Y cells as FTLD cell culture model. These FTLD neuronal cells showed intracellular aggregate formation and impaired neurite growth. Addition of PMA to culture medium 60% suppressed aggregate formation. PMA also enhanced neurite growth to the normal level at nanomolar concentration. We cultured SH-SY5Y cells in the medium containing -amyloid (1-42) as AD cell culture model. In these cells, neurite growth was limited to less than 50% of controls by the treatment of -amyloid (1-42). Surprisingly, addition of PMA increased the number of cells with >10-fold neurite extension to seven times even in -amyloid (1-42) contained medium. Also, PMA increased the expression of several genes and proteins important for cell survival in both cell culture models. These results suggest PMA has unexpected potential for the drug development against NDDs.
Medicine and Pharmacology, Neuroscience and Neurology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
