Animal models of Parkinson's disease: research status and trend analysis

Abstract

BACKGROUND: To further elucidate the etiology and pathogenesis of Parkinson's disease, standardized animal models that more closely mimic clinical conditions have garnered significant attention and achieved notable progress. OBJECTIVE: To review and summarize the current status, development trajectory, and trends in Parkinson's disease animal model research. METHODS: A total of 10 170 relevant literature from two databases, CNKI and Web of Science, were used as data samples. CiteSpace bibliometric software was then used to draw and analyze knowledge graphs of co-occurrence, clustering, emergent terms of keywords, literature publication volume, national/regional publication volume, institutional cooperation network, and literature citation in Parkinson's disease animal model research, followed by analysis. RESULTS AND CONCLUSION: The overall publication volume of Parkinson's disease animal model research, both domestically and internationally, has shown a fluctuating upward trend, with significant growth observed in the Web of Science database. China and the United States were the top publishing countries, accounting for 52.6% of total publications and emerging as primary contributors to research outcomes in this field. The leading domestic institution was Shanghai University of Traditional Chinese Medicine (131 papers), while internationally, Harvard University was the institution with the most publications (263 papers). The distribution of journals and disciplines at home and abroad is concentrated in neuroscience, neurology, molecular biology, traditional Chinese medicine, basic medicine, pharmacology, and other fields. In particular, traditional Chinese medicine treatment of Parkinson's disease has received great attention from domestic scholars, and the potential for interdisciplinary cooperation is huge. Pathological mechanisms related to Parkinson's disease animal models, such as neuroinflammation, gut microbiota, oxidative stress, mitochondrial dysfunction, and α-synuclein, are research hotspots in this field, and ferroptosis has become an emerging theme in domestic research on the mechanism of Parkinson's disease. In terms of treatment of Parkinson's disease symptoms, in addition to the continuous deepening of research on the treatment of Parkinson's disease in traditional Chinese medicine and Western medicine through animal models, new methods such as gene therapy and stem cell transplantation therapy have provided innovative therapeutic strategies in animal model research of Parkinson's disease. With the advancement of the national 'Brain Science Project' and the development of gene editing, artificial intelligence, machine learning, and brain-computer interface technology, these new technologies also have certain exploration space in Parkinson's disease research in the future.

1. Introduction

Parkinson's disease, also known as 'paralysis agitans', is a common neurodegenerative disease and the second most common neurodegenerative disorder worldwide. It typically manifests around age 60, with a prevalence of approximately 1% among individuals over 65 years [1-2]. Parkinson's disease is characterized by both motor and non-motor symptoms, including resting tremor, bradykinesia, rigidity, and postural instability [2]. The main pathological features are the degeneration of dopaminergic neurons in the substantia nigra and the aggregation of α-synuclein [3], which severely impact patients' physical and mental health. The etiology of Parkinson's disease remains incompletely understood, but research suggests that its development is associated with multiple mechanisms, such as neuroinflammation, α-synuclein aggregation, lysosomal autophagy dysfunction, mitochondrial damage, vesicle transport defects, and gut microbiota dysbiosis [4-5]. It is also linked to genetic factors, environmental factors, aging, oxidative stress, heavy metals, and head trauma, and effective treatments are still lacking [6-9]. Therefore, standardized animal models that more closely mimic clinical conditions will provide an important theoretical basis for related research.

In recent years, scholars have produced numerous academic achievements on Parkinson's disease animal models. For example, LAL et al. [10] mentioned that animal models are important experimental tools, analyzing the advantages and disadvantages of different Parkinson's disease animal models from three types: neurotoxin models, pharmacological models, and genetic models, to reproduce the mechanisms of human diseases and screen strategies for diagnosis and treatment. SUBHAN et al. [11] reviewed the characteristics of various types of Parkinson's disease animal models and compared them with human disease manifestations, discussing the research progress of Parkinson's disease animal models. HE et al. [12] analyzed traditional neurotoxin, transgenic animal, α-synuclein fiber Parkinson's models, non-human primate and non-mammalian models, as well as emerging models based on optogenetics, induced pluripotent stem cells, and gene editing, summarizing the advantages and disadvantages of various Parkinson's disease models to provide reference for model selection and clinical research. YANG Dongming et al. [13] summarized the characteristics of different animal Parkinson's disease models and compared the clinical manifestations of animal models with those of Parkinson's disease patients.