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Cryptococcus neoformans is a widespread fungal pathogen that can infect the human central nervous system (CNS) and cause fungal meningitis, leading to hundreds of thousands of deaths worldwide each year. Previous studies have demonstrated that many signal transduction pathways are crucial for the morphological development and virulence of C. neoformans. In this review, data from over 116 research articles have been compiled to show that many signaling pathways control various characteristics of C. neoformans, individually or in association with other pathways, and to establish strong links among them to better understand C. neoformans pathogenesis. Every characteristic of C. neoformans is closely linked to these signaling pathways, making this a rich area for further research. It is essential to thoroughly explore these pathways to address questions that remain and apply a molecular mechanistic approach to link them. Targeting these pathways is crucial for understanding the exact mechanism of infection pathogenesis and will facilitate the development of antifungal drugs as well as the diagnosis and prevention of cryptococcosis. [ABSTRACT FROM AUTHOR]

Cryptococcosis is a prevalent fungal infection of the central nervous system (CNS) caused by Cryptococcus neoformans, a yeast with a polysaccharide capsule in the basidiomycete group. Normally, C. neoformans infects the respiratory tract and then breaches the blood–brain 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 "Trojan horse" 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. [ABSTRACT FROM AUTHOR]