Different roads to the brain: A brief overview of divergent pathways and convergent mechanisms in amoebic neuroinvasion

Free-living amoebae such as Acanthamoeba spp., Balamuthia mandrillaris , and Naegleria fowleri are opportunistic protists capable of causing devastating infections of the central nervous system. Although these organisms differ in ecology, morphology, and clinical progression, they converge on shared strategies that enable adhesion, immune evasion, and neuroinvasion. Here, we briefly present a comparative analysis of their routes of entry, molecular determinants, and neuropathogenic mechanisms with an eye to understand parallel and divergent pathways. A complete understanding of shared and distinct mechanisms can inform translational advances, including organoid-based modelling, multi-omics biomarker discovery, and therapeutic targeting of conserved host-pathogen signalling pathways. • Free-living amoebae can cause central nervous system infections. • Distinct amoebae share strategies for adhesion, immune evasion, and neuroinvasion. • We compare entry routes, molecular determinants, and neuropathogenic mechanisms. • Mechanistic insights inform organoids, multi-omics biomarkers, and therapies.