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However, this essential metabolic pathway is highly susceptible to oxidative stress, which can lead to lipid peroxidation, a damaging process induced by reactive oxygen species. Lipid peroxidation generates by-products that disrupt many cellular functions, with a strong impact on proteostasis. In this review, we explore the role of lipid oxidation in protein folding and its associated pathological implications, with a particular focus on findings in neurodegeneration from Caenorhabditis elegans studies, an animal model that remains underutilized. Additionally, we highlight the effectiveness of different methodologies applied in this nematode to deepen our understanding of this intricate process. In the nervous system of any animal, including mammals and invertebrates, lipid oxidation can disturb the delicate balance of cellular homeostasis, leading to oxidative stress, the build-up of toxic by-products, and protein misfolding, key factors in neurodegenerative diseases. This disruption contributes to the pathogenesis of neurodegenerative disorders such as Alzheimer\u2019s, Parkinson\u2019s, or Huntington\u2019s disease. The findings from Caenorhabditis elegans studies offer valuable insights into these complex processes and highlight potential avenues for developing targeted therapies to mitigate neurodegenerative disease progression.<\/jats:p>","DOI":"10.3390\/antiox14010078","type":"journal-article","created":{"date-parts":[[2025,1,10]],"date-time":"2025-01-10T06:25:54Z","timestamp":1736490354000},"page":"78","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Lipid Oxidation at the Crossroads: Oxidative Stress and Neurodegeneration Explored in Caenorhabditis elegans"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2832-1039","authenticated-orcid":false,"given":"Julia","family":"Tortajada-P\u00e9rez","sequence":"first","affiliation":[{"name":"Laboratory of Molecular, Cellular and Genomic Biomedicine, Instituto de Investigaci\u00f3n Sanitaria La Fe, 46026 Valencia, Spain"},{"name":"Joint Unit for Rare Diseases IIS La Fe\u2014CIPF, 46026 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2823-2869","authenticated-orcid":false,"given":"Andrea del Valle","family":"Carranza","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular, Cellular and Genomic Biomedicine, Instituto de Investigaci\u00f3n Sanitaria La Fe, 46026 Valencia, Spain"},{"name":"Joint Unit for Rare Diseases IIS La Fe\u2014CIPF, 46026 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Trujillo-del R\u00edo","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular, Cellular and Genomic Biomedicine, Instituto de Investigaci\u00f3n Sanitaria La Fe, 46026 Valencia, Spain"},{"name":"Joint Unit for Rare Diseases IIS La Fe\u2014CIPF, 46026 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar","family":"Collado-P\u00e9rez","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular, Cellular and Genomic Biomedicine, Instituto de Investigaci\u00f3n Sanitaria La Fe, 46026 Valencia, Spain"},{"name":"Joint Unit for Rare Diseases IIS La Fe\u2014CIPF, 46026 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Mar\u00eda","family":"Mill\u00e1n","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular, Cellular and Genomic Biomedicine, Instituto de Investigaci\u00f3n Sanitaria La Fe, 46026 Valencia, Spain"},{"name":"Joint Unit for Rare Diseases IIS La Fe\u2014CIPF, 46026 Valencia, Spain"},{"name":"Center for Biomedical Network Research on Rare Diseases (CIBERER), Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2113-0600","authenticated-orcid":false,"given":"Gema","family":"Garc\u00eda-Garc\u00eda","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular, Cellular and Genomic Biomedicine, Instituto de Investigaci\u00f3n Sanitaria La Fe, 46026 Valencia, Spain"},{"name":"Joint Unit for Rare Diseases IIS La Fe\u2014CIPF, 46026 Valencia, Spain"},{"name":"Center for Biomedical Network Research on Rare Diseases (CIBERER), Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1594-0033","authenticated-orcid":false,"given":"Rafael Pascual","family":"V\u00e1zquez-Manrique","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular, Cellular and Genomic Biomedicine, Instituto de Investigaci\u00f3n Sanitaria La Fe, 46026 Valencia, Spain"},{"name":"Joint Unit for Rare Diseases IIS La Fe\u2014CIPF, 46026 Valencia, Spain"},{"name":"Center for Biomedical Network Research on Rare Diseases (CIBERER), Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.pneurobio.2013.08.003","article-title":"A Review of Quality of Life after Predictive Testing for and Earlier Identification of Neurodegenerative Diseases","volume":"110","author":"Paulsen","year":"2013","journal-title":"Prog. 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