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Normally, C. neoformans infects the respiratory tract and then breaches the blood\u2013brain barrier (BBB), leading to meningitis or meningoencephalitis, which leads to hundreds of thousands of deaths each year. Although the mechanism by which C. neoformans infiltrates the BBB to invade the brain has yet to be fully understood, research has revealed that C. neoformans can cross the BBB using transcellular penetration, paracellular traversal, and infected phagocytes (the \u201cTrojan horse\u201d mechanism). The secretion of multiple virulence factors by C. neoformans is crucial in facilitating the spread of infection after breaching the BBB and causing brain infections. Extensive research has shown that various virulence factors play a significant role in the dissemination of infection beyond the lungs. This review explores the mechanisms of C. neoformans entering the CNS and explains how it bypasses the BBB. Additionally, it aims to understand the interplay between the regulatory mechanisms and virulence factors of C. neoformans.<\/jats:p>","DOI":"10.3390\/jof10080586","type":"journal-article","created":{"date-parts":[[2024,8,19]],"date-time":"2024-08-19T06:41:31Z","timestamp":1724049691000},"page":"586","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Mechanisms and Virulence Factors of Cryptococcus neoformans Dissemination to the Central Nervous System"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-7342-4259","authenticated-orcid":false,"given":"Ammar Mutahar","family":"Al-Huthaifi","sequence":"first","affiliation":[{"name":"Medical Research Institute, Southwest University, Chongqing 400715, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8768-9821","authenticated-orcid":false,"given":"Bakeel A.","family":"Radman","sequence":"additional","affiliation":[{"name":"Cancer Center, Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510315, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2473-5020","authenticated-orcid":false,"given":"Abdullah Ali","family":"Al-Alawi","sequence":"additional","affiliation":[{"name":"Medical Research Institute, Southwest University, Chongqing 400715, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fawad","family":"Mahmood","sequence":"additional","affiliation":[{"name":"Medical Research Institute, Southwest University, Chongqing 400715, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9111-8826","authenticated-orcid":false,"given":"Tong-Bao","family":"Liu","sequence":"additional","affiliation":[{"name":"Medical Research Institute, Southwest University, Chongqing 400715, China"},{"name":"Jinfeng Laboratory, Chongqing 401329, China"},{"name":"Engineering Research Center for Cancer Biomedical and Translational Medicine, Southwest University, Chongqing 400715, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Oliveira, J., Radhouani, H., and Reis, R.L. 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