Ting Yu, Qingxin Mai, Qian Wang, Mingxia Pan, Yuanfang Xiong, Lingyu Kuang, Hanjiao Liu
PD is a multifactorial neurodegenerative disorder characterized by complex and heterogeneous pathological mechanisms, supporting the exploration of multi-target therapeutic strategies. GLP-1 receptor signaling is widely distributed in the central nervous system and peripheral metabolic tissues, suggesting a potential link between metabolic regulation and neurodegenerative processes. Bibliometric analysis indicates that GLP-1 receptor agonists have attracted increasing research attention in PD, particularly in relation to metabolic dysfunction, neuroinflammation, and mitochondrial pathways. However, current clinical evidence remains inconsistent, with findings influenced by drug heterogeneity, study populations, and methodological differences. Overall, GLP-1 receptor-related mechanisms represent an emerging and evolving research direction in PD, warranting further experimental and clinical investigation.
BACKGROUND: PD is still managed symptomatically with levodopa, and no disease-modifying therapy is available, making effective treatment difficult. In recent years, preclinical and some clinical evidence have shown that glucagon-like peptide-1 receptor agonists (GLP-1 receptor agonists, GLP-1 RAs) can cross to varying degrees the blood-brain barrier and exert neuroprotective effects, including anti-inflammatory, antioxidant, and insulin-sensitizing actions. They also reduce pathological protein aggregation, regulate mitochondrial function, and enhance autophagy, demonstrating their therapeutic potential for PD. Therefore, systematically reviewing the research status, hotspots, and trends of GLP-1 receptor agonists in PD is crucial for understanding the dynamic development of this field.
METHODS: Systematic searches were performed in the Web of Science Core Collection and Scopus databases to identify literature on GLP-1 receptor agonists and PD. Bibliometric analyses were conducted using CiteSpace and VOSviewer to evaluate publication trends, collaborative networks, co-citation patterns, and research hotspots. The search period spanned from database inception to April 14, 2026.
RESULTS: A total of 282 articles from WoS and Scopus were included for bibliometric analysis. The top three countries are China, the United States, and the United Kingdom. Major institutions include University College London, Shanxi Medical University, Henan University of Chinese Medicine, and Lancaster University, with authors Hölscher, Athauda, Aviles-Olmos, and Li. Hotspots focus on oxidative stress, insulin resistance, alpha-synuclein, blood-brain barrier, and exendin-4. Emerging themes with increasing research attention include mild cognitive impairment, GIP/GLP-1 dual agonists, and blood-brain barrier.
CONCLUSION: PD is a multifactorial neurodegenerative disorder characterized by complex and heterogeneous pathological mechanisms, supporting the exploration of multi-target therapeutic strategies. GLP-1 receptor signaling is widely distributed in the central nervous system and peripheral metabolic tissues, suggesting a potential link between metabolic regulation and neurodegenerative processes. Bibliometric analysis indicates that GLP-1 receptor agonists have attracted increasing research attention in PD, particularly in relation to metabolic dysfunction, neuroinflammation, and mitochondrial pathways. However, current clinical evidence remains inconsistent, with findings influenced by drug heterogeneity, study populations, and methodological differences. Overall, GLP-1 receptor-related mechanisms represent an emerging and evolving research direction in PD, warranting further experimental and clinical investigation.
SYSTEMATIC REVIEW REGISTRATION: https://osf.io/u7wdy.