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Antibody-recognizing residues 188-211 of TMEM106B exhibit immunohistochemical reactivity with the TMEM106B C-terminal fragment

Accumulation of TMEM106B fibrils composed of cleaved C-terminal fragments (CTF) of transmembrane protein 106B (TMEM106B) has recently been observed in the brains of elderly subjects and individuals with neurodegenerative diseases. To date, one antibody recognizing the residues 239-250 has been found...

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Autores principales: Ishikawa, Ruoyi, Yamazaki, Yu, Nakamori, Masahiro, Takahashi, Tetsuya, Maruyama, Hirofumi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10626444/
https://www.ncbi.nlm.nih.gov/pubmed/37937069
http://dx.doi.org/10.3389/fnins.2023.1250547
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author Ishikawa, Ruoyi
Yamazaki, Yu
Nakamori, Masahiro
Takahashi, Tetsuya
Maruyama, Hirofumi
author_facet Ishikawa, Ruoyi
Yamazaki, Yu
Nakamori, Masahiro
Takahashi, Tetsuya
Maruyama, Hirofumi
author_sort Ishikawa, Ruoyi
collection PubMed
description Accumulation of TMEM106B fibrils composed of cleaved C-terminal fragments (CTF) of transmembrane protein 106B (TMEM106B) has recently been observed in the brains of elderly subjects and individuals with neurodegenerative diseases. To date, one antibody recognizing the residues 239-250 has been found to display immunoreactivity to the TMEM106B CTF, thereby defining TMEM106B C-terminal immunoreactive (TMEM-ir) material. Immunohistochemical characterization of the CTF using antibodies targeting different immunogens could further shed light on the attributes of TMEM-ir material and the biological relevance of TMEM106B fibril accumulation in vivo. Therefore, we generated and validated five polyclonal antibodies against distinct CTF immunogens, namely the residues 140-163, 164-187, 188-211, 239-250, and 253-274. The antibody recognizing the residues 239-250 (antibody no. 5: 239-250) was employed to identify cases positive for TMEM-ir material. Among the remaining four antibodies, antibody no. 3: 188-211 exhibited significant immunoreactivity in TMEM-ir material-positive cases. Comparative analyzes indicated that antibody no. 3: 188-211 and antibody no. 5: 239-250 likely recognized the same TMEM-ir material. The TMEM-ir material detected by antibody no. 3: 188-211 was observed across multiple brain cell types without co-localization with other pathogenic proteins. In conclusion, our findings suggest that the antibody recognizing the residues 188-211 displays immunohistochemical reactivity to TMEM-ir material. Therefore, in addition to the established antibody recognizing the residues 239-250, the antibody recognizing the residues 188-211 can potentially be used in immunohistochemical studies to further elucidate the significance of CTF accumulation in the brain.
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spelling pubmed-106264442023-11-07 Antibody-recognizing residues 188-211 of TMEM106B exhibit immunohistochemical reactivity with the TMEM106B C-terminal fragment Ishikawa, Ruoyi Yamazaki, Yu Nakamori, Masahiro Takahashi, Tetsuya Maruyama, Hirofumi Front Neurosci Neuroscience Accumulation of TMEM106B fibrils composed of cleaved C-terminal fragments (CTF) of transmembrane protein 106B (TMEM106B) has recently been observed in the brains of elderly subjects and individuals with neurodegenerative diseases. To date, one antibody recognizing the residues 239-250 has been found to display immunoreactivity to the TMEM106B CTF, thereby defining TMEM106B C-terminal immunoreactive (TMEM-ir) material. Immunohistochemical characterization of the CTF using antibodies targeting different immunogens could further shed light on the attributes of TMEM-ir material and the biological relevance of TMEM106B fibril accumulation in vivo. Therefore, we generated and validated five polyclonal antibodies against distinct CTF immunogens, namely the residues 140-163, 164-187, 188-211, 239-250, and 253-274. The antibody recognizing the residues 239-250 (antibody no. 5: 239-250) was employed to identify cases positive for TMEM-ir material. Among the remaining four antibodies, antibody no. 3: 188-211 exhibited significant immunoreactivity in TMEM-ir material-positive cases. Comparative analyzes indicated that antibody no. 3: 188-211 and antibody no. 5: 239-250 likely recognized the same TMEM-ir material. The TMEM-ir material detected by antibody no. 3: 188-211 was observed across multiple brain cell types without co-localization with other pathogenic proteins. In conclusion, our findings suggest that the antibody recognizing the residues 188-211 displays immunohistochemical reactivity to TMEM-ir material. Therefore, in addition to the established antibody recognizing the residues 239-250, the antibody recognizing the residues 188-211 can potentially be used in immunohistochemical studies to further elucidate the significance of CTF accumulation in the brain. Frontiers Media S.A. 2023-10-23 /pmc/articles/PMC10626444/ /pubmed/37937069 http://dx.doi.org/10.3389/fnins.2023.1250547 Text en Copyright © 2023 Ishikawa, Yamazaki, Nakamori, Takahashi and Maruyama. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Ishikawa, Ruoyi
Yamazaki, Yu
Nakamori, Masahiro
Takahashi, Tetsuya
Maruyama, Hirofumi
Antibody-recognizing residues 188-211 of TMEM106B exhibit immunohistochemical reactivity with the TMEM106B C-terminal fragment
title Antibody-recognizing residues 188-211 of TMEM106B exhibit immunohistochemical reactivity with the TMEM106B C-terminal fragment
title_full Antibody-recognizing residues 188-211 of TMEM106B exhibit immunohistochemical reactivity with the TMEM106B C-terminal fragment
title_fullStr Antibody-recognizing residues 188-211 of TMEM106B exhibit immunohistochemical reactivity with the TMEM106B C-terminal fragment
title_full_unstemmed Antibody-recognizing residues 188-211 of TMEM106B exhibit immunohistochemical reactivity with the TMEM106B C-terminal fragment
title_short Antibody-recognizing residues 188-211 of TMEM106B exhibit immunohistochemical reactivity with the TMEM106B C-terminal fragment
title_sort antibody-recognizing residues 188-211 of tmem106b exhibit immunohistochemical reactivity with the tmem106b c-terminal fragment
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10626444/
https://www.ncbi.nlm.nih.gov/pubmed/37937069
http://dx.doi.org/10.3389/fnins.2023.1250547
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