Fragile X-associated tremor ataxia syndrome with co-occurrent progressive supranuclear palsy-like neuropathology
Fragile X-associated tremor ataxia syndrome with co-occurrent progressive supranuclear palsy-like neuropathology. neuronal inclusions (54C56). Ubiquitin has also historically been used as tool for detecting such inclusions. Both p62 and ubiquitin represent components of cellular UPS, and as such, can be used in a similar capacity to highlight aberrant protein accumulation that have been ZSTK474 labeled for degradation. However, ubiquitin antibodies consistently exhibit extensive reactivity within background tissue, and have been documented to show lower intensity labeling of diagnostic inclusions as compared with p62 (22). By virtue of its reduced immunoreactivity for nonspecific background structures, p62 provides a superior tool for the identification of inclusions for which specific antibodies are ZSTK474 not currently widely available. Conclusion We introduce 2 novel mouse monoclonal antibodies for p62, 5G3 and 2A5, raised against residues 360C380 of human p62. ZSTK474 These antibodies have demonstrated a unique ZSTK474 ability to highlight specific types of deposits across neurodegenerative disease types. In addition to serving as tools for investigations into the role of p62 in protein aggregation disorders, these antibodies may find practical use as tools for diagnosing C9orf72-repeat expansion disorders, as well as potentially other repeat-expansion disorders for which protein-specific antibodies are not readily available. Supplementary Material nlaa007_Supplementary_DataClick here for additional data file.(22M, zip) These studies were supported by grants NS089622 and “type”:”entrez-nucleotide”,”attrs”:”text”:”AG047266″,”term_id”:”16584158″,”term_text”:”AG047266″AG047266 from the National Institutes of Health. ZAS received support from F30AG063446. Tissue samples were supplied by the University of Florida Neuromedicine Human Brain Tissue Bank and the Mayo Clinic ADRC (P30 AG062677). The authors have no duality or conflicts of interest to declare. Recommendations 1. Ross CA, Poirier MA.. Protein aggregation and neurodegenerative disease. Nat Med 2004;10:S10C7 [PubMed] [Google Scholar] 2. Golde TE, Borchelt DR, Giasson BI, et al. Thinking laterally about neurodegenerative proteinopathies. J Clin Invest 2013;123:1847C55 [PMC free article] [PubMed] [Google Scholar] 3. Spires-Jones TL, Attems J, Thal DR.. Relationships of pathological proteins in neurodegenerative diseases. Acta Neuropathol 2017;134:187C205 [PMC free article] [PubMed] [Google Scholar] 4. Braak H, Alafuzoff I, Arzberger T, et al. Staging of Alzheimer disease-associated neurofibrillary pathology using paraffin sections and immunocytochemistry. Acta Neuropathol 2006;112:389C404 [PMC free article] [PubMed] [Google Scholar] 5. Beach TG, White colored CL, Hamilton RL, et al. Evaluation of -synuclein immunohistochemical methods used by invited specialists. Acta Neuropathol 2008;116:277C88 [PMC free article] [PubMed] [Google Scholar] Rock2 6. Banez-Coronel M, Ranum LPW.. Repeat-associated non-AUG (RAN) translation: Insights from pathology. Lab Invest 2019;99:929C42 [PMC free article] [PubMed] [Google Scholar] 7. Komatsu M, Kageyama S, Ichimura Y.. Invited review p62/SQSTM1/A170: Physiology and pathology. Pharmacol Res 2012;66:457C62 [PubMed] [Google Scholar] 8. Wooten MW, Hu X, Babu JR, et al. Signaling, polyubiquitination, trafficking, and inclusions: Sequestosome 1/p62s part in neurodegenerative disease. J Biomed Biotechnol 2006;2006:1C12. [PMC free article] [PubMed] [Google Scholar] 9. Jin Z, Li Y, Pitti R, et al. Cullin3-centered polyubiquitination and p62-dependent aggregation of caspase-8 mediate extrinsic apoptosis signaling. Cell 2009;137:721C35 [PubMed] [Google Scholar] ZSTK474 10. Moscat J, Diaz-Meco MT, Wooten MW.. Transmission integration and diversification through the p62 scaffold protein. Styles Biochem Sci 2007;32:95C100 [PubMed] [Google Scholar] 11. Takamura A, Komatsu M, Hara T, et al. Autophagy-deficient mice develop multiple liver tumors. Genes Dev 2011;25:795C800 [PMC free article] [PubMed] [Google Scholar] 12. Duran A, Linares JF, Galvez AS, et al. The signaling adaptor p62 is an important NF-B mediator in tumorigenesis. Malignancy Cell 2008;13:343C54 [PubMed] [Google Scholar].