{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T04:59:35Z","timestamp":1792213175988,"version":"4.4.0"},"reference-count":58,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2024,5,16]],"date-time":"2024-05-16T00:00:00Z","timestamp":1715817600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001411","name":"ICMR","doi-asserted-by":"crossref","award":["BMI\/11(63)\/2020"],"award-info":[{"award-number":["BMI\/11(63)\/2020"]}],"id":[{"id":"10.13039\/501100001411","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001411","name":"ICMR","doi-asserted-by":"crossref","award":["DHR\/Neuro\/2020-NCD-I"],"award-info":[{"award-number":["DHR\/Neuro\/2020-NCD-I"]}],"id":[{"id":"10.13039\/501100001411","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>Amyotrophic lateral sclerosis (ALS) is a relentlessly progressive and fatal neurodegenerative diseases for which at present no cure is available. Despite the extensive research the progress from diagnosis to prognosis in ALS and frontotemporal dementia (FTD) has been slow which represents suboptimal understanding of disease pathophysiological processes. In recent studies, several genes have been associated with the ALS and FTD diseases such as SOD1, TDP43, and TBK1, whereas the hexanucleotide GGGGCC repeat expansion (HRE) in <jats:italic>C9orf72<\/jats:italic> gene is a most frequent cause of ALS and FTD, that has changed the understanding of these diseases.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>The goal of this study was to identify and spatially determine differential gene expression signature differences between cerebellum and frontal cortex in C9orf72-associated ALS (C9-ALS), to study the network properties of these differentially expressed genes, and to identify miRNAs targeting the common differentially expressed genes in both the tissues. This study thus highlights underlying differential cell susceptibilities to the disease mechanisms in C9-ALS and suggesting therapeutic target selection in C9-ALS.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>In this manuscript, we have identified that the genes involved in neuron development, protein localization and transcription are mostly enriched in cerebellum of C9-ALS patients, while the UPR-related genes are enriched in the frontal cortex. Of note, UPR pathway genes were mostly dysregulated both in the C9-ALS cerebellum and frontal cortex. Overall, the data presented here show that defects in normal RNA processing and the UPR pathway are the pathological hallmarks of C9-ALS. Interestingly, the cerebellum showed more strong transcriptome changes than the frontal cortex.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusion<\/jats:title>\n<jats:p>Interestingly, the cerebellum region showed more significant transcriptomic changes as compared to the frontal cortex region suggesting its active participation in the disease process. This nuanced understanding may offer valuable insights for the development of targeted therapeutic strategies aimed at mitigating disease progression in C9-ALS.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0301267","type":"journal-article","created":{"date-parts":[[2024,5,16]],"date-time":"2024-05-16T17:57:03Z","timestamp":1715882223000},"page":"e0301267","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":3,"title":["Understanding the relationship between cerebellum and the frontal-cortex region of C9orf72-related amyotrophic lateral sclerosis: A comparative analysis of genetic features"],"prefix":"10.1371","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8730-0967","authenticated-orcid":true,"given":"Kartikay","family":"Prasad","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Md Imtaiyaz","family":"Hassan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saurabh","family":"Raghuvanshi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3621-5025","authenticated-orcid":true,"given":"Vijay","family":"Kumar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,5,16]]},"reference":[{"issue":"10107","key":"pone.0301267.ref001","doi-asserted-by":"crossref","first-page":"2084","DOI":"10.1016\/S0140-6736(17)31287-4","article-title":"Amyotrophic lateral sclerosis","volume":"390","author":"M.A. van Es","year":"2017","journal-title":"Lancet"},{"issue":"22","key":"pone.0301267.ref002","doi-asserted-by":"crossref","first-page":"1688","DOI":"10.1056\/NEJM200105313442207","article-title":"Amyotrophic lateral sclerosis","volume":"344","author":"L.P. 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