An Integrated Review of Parkinson’s Disease: Etiology, Differential Diagnosis, Biomarkers, Emerging Therapeutic Approaches, and Translational Models

Aims and Objectives: This review aims to provide a comprehensive overview of risk factors, biomarkers, pathophysiology, and synthesis of experimental models of Parkinson’s Disease (PD), with an emphasis on their mechanisms and translational models. Materials and Methods: A narrative review methodology was employed, involving an extensive literature search using databases such as PubMed, Scopus, and Web of Science. Peer-reviewed articles published up to 2025 were included. Results: Pre-clinical and clinical research has provided evidence that has enabled the decoding of Parkinson’s Disease (PD) and a breakthrough in its management/treatment. Despite the underlying mechanism not being fully understood, we now have a better interpretation of its sophisticated nature. This article highlights risk factors, some of which may be considered normal ageing but need to be addressed; diagnostic biomarkers, some of which help differentiate PD from Parkinsonism, others, less invasive, identify at-risk individuals, and neuroinflammation. This article also highlights the different pathophysiology, which also helps to emphasis the heterogeneous nature. It highlights the diverse experimental PD models because no one model fully represents PD and the research work that has been reported. This may help one to understand “the missing pieces of the puzzle”, with a note that the precision medicine framework may play a crucial role in benefiting and transforming the lives of people living with Parkinson’s Disease. Conclusions: There is no single model that fully recapitulates all aspects of PD. However, the strategic selection or combination of models can provide valuable insights into disease mechanisms and treatment efficacy. Future directions should focus on refining models that mimic progressive and heterogeneous disease features, integrating multi-omics approaches, and validating biomarkers for clinical translation. A precision medicine framework may ultimately transform PD management by linking experimental data to patient-specific therapeutic strategies.