Parkinson's disease and brain insulin signaling: Mechanisms and potential role of GLP-1 mimetics

Foroozanmehr B., Hemmati M. A., Yaribeygi H., KARAV S., Jamialahmadi T., Sahebkar A.

Brain Research, vol.1862, 2025 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Review
  • Volume: 1862
  • Publication Date: 2025
  • Doi Number: 10.1016/j.brainres.2025.149738
  • Journal Name: Brain Research
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, PASCAL, Animal Behavior Abstracts, Aquatic Science & Fisheries Abstracts (ASFA), BIOSIS, CAB Abstracts, Chemical Abstracts Core, EMBASE, Linguistics & Language Behavior Abstracts, Psycinfo, Veterinary Science Database
  • Keywords: Brain insulin signaling, Diabetes mellitus, GLP-1 mimetics, Parkinson's disease
  • Çanakkale Onsekiz Mart University Affiliated: Yes

Abstract

Parkinson's disease (PD) is a common neurodegenerative disorder characterized primarily by the degeneration of dopaminergic neurons in the substantia nigra pars compacta. The pathophysiology of PD is complex and multifactorial involving genetic factors, oxidative stress, mitochondrial dysfunction, impaired protein clearance, and neuroinflammation but recent evidence emphasizes the role of impaired brain insulin signaling. Insulin is a metabolic hormone with extensive effects on metabolic substrates but recent studies have demonstrated that it is also involved in central signaling pathways and induces different brain areas related to food craving, motor activities, cognitive abilities, and emotional feelings. Hence, it has been suggested that induction of brain insulin sensitivity may be a promising treatment for PD. Glucagon-like peptide-1 (GLP-1) mimetics are a new-generation class of antidiabetics that normalize glucose homeostasis via several pathways. Recent studies suggest extra-glycemic benefits for GLP-1 mimetics against PD. GLP-1 mimetics can prevent or slow PD progression. Additionally, these agents can improve cognitive functions by improving brain insulin signaling pathways. In this review, we aim to highlight the role of brain insulin signaling in PD pathophysiology and discuss the possible benefits of GLP-1 mimetics in PD management.