{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,9,20]],"date-time":"2024-09-20T16:47:45Z","timestamp":1726850865002},"reference-count":0,"publisher":"Negah Scientific Publisher","issue":"2","content-domain":{"domain":["www.niscpub.com"],"crossmark-restriction":false},"short-container-title":["BCN"],"abstract":"<jats:p>Introduction: Profilin1 (PFN1) is a ubiquitously expressed protein known for its function as a regulator of actin polymerization and dynamics. A recent discovery linked mutant PFN1 to Amyotrophic Lateral Sclerosis (ALS), which is a fatal and progressive motor neuron disease. We have also demonstrated that Gly118Val mutation in PFN1 is a cause of ALS, and the formation of aggregates containing mutant PFN1 may be a mechanism for motor neuron death. Hence, we were interested in investigating the aggregation of PFN1 further and searching for co-aggregated proteins in our mouse model overexpressing mutant PFN1. Methods: We investigated protein aggregation in several tissues of transgenic and no-transgenic mice using western blotting. To further understand the neurotoxicity of mutant PFN1, we conducted a pull-down assay using an insoluble fraction of spinal cord lysates from hPFN1G118V transgenic mice. For this assay, we expressed His6-tagged PFN1WT and PFN1G118V in E. coli and purified these proteins using the Ni-NTA column. Results: In this study, we demonstrated that mutant PFN1 forms aggregate in the brain and spinal cord of hPFN1G118V mice, while WT-PFN1 remains soluble. Among these tissues, spinal cord lysates were found to have PFN1 bands at higher molecular weights recognized with anti-PFN1. Moreover, the pull-down assay using His6-PFN1G118V showed that Myelin Binding Protein (MBP) was present in the insoluble fraction. Conclusion: Our analysis of PFN1 aggregation in vivo revealed further details of mutant PFN1 aggregation and its possible complex formation with other proteins, providing new insights into the ALS mechanism.<\/jats:p>","DOI":"10.32598\/bcn.12.2.1631.1","type":"journal-article","created":{"date-parts":[[2021,5,25]],"date-time":"2021-05-25T08:36:02Z","timestamp":1621931762000},"page":"213-222","update-policy":"http:\/\/dx.doi.org\/10.32598\/nsp.crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Mutant Profilin1 Aggregation in Amyotrophic Lateral Sclerosis: An in Vivo Biochemical Analysis"],"prefix":"10.32598","volume":"12","author":[{"name":"Department of Phytochemistry, Medicinal Plants and Drugs Research Institute, Shahid Beheshti University, Tehran, Iran.","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mina","family":"Nekouei","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Atousa","family":"Aliahmadi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"Department of Biology, Medicinal Plants and Drugs Research Institute, Shahid Beheshti University, Tehran, Iran.","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mahmoud","family":"Kiaei","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"Department of Pharmacology and Toxicology, Department of Neurology, Department of Geriatrics, University of Arkansas for Medical Sciences, Little Rock, USA.","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ali Reza","family":"Ghassempour","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"Department of Phytochemistry, Medicinal Plants and Drugs Research Institute, Shahid Beheshti University, Tehran, Iran.","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"17540","published-online":{"date-parts":[[2021,3,1]]},"container-title":["Basic and Clinical Neuroscience Journal"],"original-title":[],"link":[{"URL":"http:\/\/bcn.iums.ac.ir\/article-1-1383-en.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,5,25]],"date-time":"2021-05-25T08:36:08Z","timestamp":1621931768000},"score":1,"resource":{"primary":{"URL":"http:\/\/bcn.iums.ac.ir\/article-1-1383-en.html"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,1]]},"references-count":0,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2021,3,1]]}},"URL":"https:\/\/doi.org\/10.32598\/bcn.12.2.1631.1","relation":{},"ISSN":["2228-7442","2008-126X"],"issn-type":[{"type":"print","value":"2228-7442"},{"type":"electronic","value":"2008-126X"}],"subject":[],"published":{"date-parts":[[2021,3,1]]}}}