{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T03:53:39Z","timestamp":1787025219375,"version":"build-2736575974"},"reference-count":0,"publisher":"Polish Academy of Sciences Chancellery","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>Introduction: Amyotrophic lateral sclerosis (ALS) represents a heterogeneous group of neurodegenerative disorders sharing a common ALS phenotype but arising from diverse genetic and molecular mechanisms. Among the genes implicated in ALS, SQSTM1, encoding the multifunctional protein p62, plays a pivotal role in maintaining neuronal homeostasis through the regulation of autophagy and the crosstalk between NF-\u03baB and Nrf2 pathways. Disruption of these mechanisms contributes to oxidative stress, neuroinflammation, and protein aggregation in motor neurons. Material and Methods: A comprehensive genetic analysis, including next-generation sequencing (NGS), whole-exome sequencing (WES), and multiplex ligation-dependent probe amplification (MLPA), was performed in a patient clinically diagnosed with ALS. Literature data regarding the role of SQSTM1, NF-\u03baB\/ Nrf2 signaling, and autophagy modulation in ALS pathogenesis were reviewed to contextualize the findings. Case Presentation: We describe a 49-year-old woman with a 12-month history of progressive bulbar- onset ALS. Genetic testing revealed a heterozygous SQSTM1 c.1175C&amp;gt;T (p.Pro392Leu) variant inherited from her father, classified as likely pathogenic. The patient received dimethyl fumarate (Nrf2 activator), celecoxib ( NF-\u03baB inhibitor), and rapamycin (mTOR pathway modulator) as part of an individualized treatment strategy. Discussion: Mutations in SQSTM1 contribute to ALS pathogenesis through dysregulation of autophagy, impaired protein clearance, and excessive neuroinflammation mediated by NF-\u03baB activation. The interplay between NF-\u03baB and Nrf2 signaling pathways suggests that targeted therapeutic modulation may attenuate neurodegeneration. The patient\u2019s case illustrates the clinical and molecular heterogeneity of ALS and supports the concept of pathway-specific, precision medicine approaches. Conclusions: This case highlights the relevance of SQSTM1-related pathogenic mechanisms within the heterogeneous ALS spectrum and underscores the importance of advanced genetic testing for identifying candidates for personalized therapy.<\/jats:p>","DOI":"10.24425\/fmc.2025.156692","type":"journal-article","created":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T10:29:31Z","timestamp":1765880971000},"page":"173-173","source":"Crossref","is-referenced-by-count":1,"title":["A case of an ALS patient with an SQSTM1 mutation \u2014 implications for the p62\/NF-\u03baB\/Nrf2\/autophagy pathways in the selection of individualised therapeutic strategies: a preliminary report"],"prefix":"10.24425","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9214-3022","authenticated-orcid":false,"given":"Kamila","family":"\u017bur-Wyrozumska","sequence":"first","affiliation":[{"name":"Center for Innovative Medical Education, Jagiellonian University Medical College, Krak\u00f3w, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"37468","published-online":{"date-parts":[[2025,9,30]]},"container-title":["Folia Medica Cracoviensia"],"original-title":[],"language":"pl","link":[{"URL":"https:\/\/journals.pan.pl\/Content\/137617\/PDF\/173-183-Folia%20Medica%2003-2025-i-14.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T10:30:30Z","timestamp":1765881030000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.pan.pl\/dlibra\/publication\/156692\/edition\/137617\/content"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,30]]},"references-count":0,"URL":"https:\/\/doi.org\/10.24425\/fmc.2025.156692","relation":{},"ISSN":["0015-5616"],"issn-type":[{"value":"0015-5616","type":"print"}],"subject":[],"published":{"date-parts":[[2025,9,30]]}}}