Decoding Parkinson’s Disease through Animal Models: Mechanistic Insights and Therapeutic Roadmaps
Year: 2025
Type: article
Abstract: Parkinson’s disease (PD) is a complex neurodegenerative disorder characterized by progressive dopaminergic neuronal loss, α-synuclein aggregation, and a range of motor and non-motor symptoms. Animal models have been indispensable in elucidating PD mechanisms and testing therapeutic strategies; however, no single model fully recapitulates the multifaceted human pathology. This review presents a comprehensive and comparative analysis of neurotoxic (e.g., 6-OHDA, MPTP, rotenone), genetic (e.g., α-synuclein, LRRK2, PINK1, Parkin, DJ-1), and pharmacological (e.g., reserpine, haloperidol) models of PD. We highlight each model’s mechanistic relevance, behavioural features, and limitations, particularly regarding non-motor symptoms, disease progression, and translational applicability. Special focus is given to the emerging use of humanized models, iPSC-based systems, and multi-hit protocols that combine genetic and environmental factors. Novel dimensions such as sex differences, the gut-brain axis, peripheral pathology, and immune system involvement are critically examined. Furthermore, the integration of biomarkers (e.g., phosphorylated α-synuclein, DJ-1, cytokines) and advanced imaging tools (PET, MRI) is discussed as a refinement in model validation and disease monitoring. We also explore how AI-driven approaches can enhance data analysis and predictive modelling. By synthesizing traditional and emerging insights, this review provides a multidimensional perspective on PD modelling. It underscores the need for strategic, integrative model selection to bridge preclinical research with clinical translation and to facilitate the development of effective, personalized therapies.
Authors: Chandrika G V, Bhagya V Rao
Institution: KLE Academy of Higher Education and Research
Language: English
Subfield: Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
OpenAlex ID: W4410152620