Unconventional Non-rodent Models in Neurological Research: Exploring New Paths to Translational Insights

Abstract

Neurological disorders such as Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), Schizophrenia (SCZ), and epilepsy pose a significant global health challenge, particularly among the ageing population. With Alzheimer’s cases projected to double in the next 30 years, the lack of effective treatments presents a critical concern, leading to substantial social and economic burdens. While rodent models have been instrumental in elucidating disease mechanisms and identifying therapeutic targets, their limited translational success necessitates exploring alternative model systems. This review highlights the increasing integration of non-rodent models, including invertebrates (Drosophila melanogaster and Caenorhabditis elegans), lower vertebrates (Danio rerio), and higher-order mammals (non-human primates), alongside emerging approaches such as Octopus models, 2D and 3D cell culture systems, computational models, and in silico methodologies. These alternative models provide unique advantages in studying neural development, function, and pathology, offering improved translational relevance. By leveraging the complementary strengths of these systems, researchers can refine therapeutic strategies and advance our understanding of complex neurological disorders.

Graphical Abstract