{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T16:30:27Z","timestamp":1791304227795,"version":"4.3.1"},"reference-count":81,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T00:00:00Z","timestamp":1772236800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Anderson\u2013Fabry disease (FD) is an X-linked lysosomal storage disorder caused by pathogenic variants in the GLA gene, resulting in deficient \u03b1-galactosidase A activity and progressive accumulation of globotriaosylceramide (Gb3) and its derivative lyso-Gb3 within lysosomes. Beyond substrate storage, FD involves a complex interplay of molecular, metabolic, and inflammatory disturbances that collectively drive multisystemic damage. It seems that Gb3 accumulation impairs autophagic flux, promotes mitochondrial dysfunction, and triggers endoplasmic reticulum stress, leading to oxidative imbalance and bioenergetic failure. Concurrently, activation of innate immune pathways, particularly the TLR4\/NF-\u03baB axis, induces pro-inflammatory cytokine release and endothelial dysfunction, while complement activation and adaptive immune responses contribute to chronic inflammation and fibrosis. These mechanisms define a sustained state of \u201cmetaflammation,\u201d linking lysosomal dysfunction to systemic inflammation. Understanding this molecular cross-talk provides a rationale for identifying novel biomarkers and designing therapies that go beyond enzymatic correction, including chaperone therapy, substrate reduction, and gene-based or anti-inflammatory approaches. A deeper comprehension of these interconnected patterns may guide the development of precision medicine strategies aimed at improving long-term outcomes in Fabry disease.<\/jats:p>","DOI":"10.3390\/cells15050443","type":"journal-article","created":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T16:06:59Z","timestamp":1772467619000},"page":"443","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Molecular, Metabolic and Inflammatory Patterns Involved in Pathogenesis of Anderson-Fabry Disease"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1574-104X","authenticated-orcid":false,"given":"Irene","family":"Simonetta","sequence":"first","affiliation":[{"name":"Internal Medicine and Stroke Care Ward, Regional Reference Center for Diagnosis and Treatment of Anderson-Fabry Disease, Department of Health Promotion, Maternal and Child Health, Internal Medicine and Specialty Excellence \u201cG. D\u2019Alessandro\u201d (PROMISE), University of Palermo, Piazza delle Cliniche n.2, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Baglio","sequence":"additional","affiliation":[{"name":"Internal Medicine and Stroke Care Ward, Regional Reference Center for Diagnosis and Treatment of Anderson-Fabry Disease, Department of Health Promotion, Maternal and Child Health, Internal Medicine and Specialty Excellence \u201cG. D\u2019Alessandro\u201d (PROMISE), University of Palermo, Piazza delle Cliniche n.2, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6440-7318","authenticated-orcid":false,"given":"Antonino","family":"Tuttolomondo","sequence":"additional","affiliation":[{"name":"Internal Medicine and Stroke Care Ward, Regional Reference Center for Diagnosis and Treatment of Anderson-Fabry Disease, Department of Health Promotion, Maternal and Child Health, Internal Medicine and Specialty Excellence \u201cG. D\u2019Alessandro\u201d (PROMISE), University of Palermo, Piazza delle Cliniche n.2, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Li, X., Ren, X., Zhang, Y., Ding, L., Huo, M., and Li, Q. (2022). Fabry Disease: Mechanism and Therapeutics Strategies. Front. 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