The therapeutic effects and mechanisms of glucagon-like peptide-1 receptor agonists in neurocognitive disorders

• Published in: Therapeutic advances in neurological disorders Vol. 18; p. 17562864251332035
• Main Authors: Si, Junchen, Yu, Kai, Hao, Jiheng, Wang, Jiyue, Zhang, Liyong
• Format: Journal Article
• Language: English
• Published: England SAGE Publications 01.01.2025; SAGE Publishing
• Subjects: Review; neurocognitive disorders; neuroinflammation; chronic cerebral hypoperfusion; neuroprotective; glucagon-like peptide-1 (GLP-1)
• ISSN: 1756-2864; 1756-2856; 1756-2864
• DOI: 10.1177/17562864251332035

Chronic cerebral hypoperfusion (CCH) represents a key pathogenic contributor to neurocognitive disorders. It can lead to multifaceted pathological alterations including neuroinflammation, neuronal apoptosis, blood–brain barrier disruption, synaptic plasticity deficits, and mitochondrial dysfunction. The glucagon-like peptide-1 receptor (GLP-1R), ubiquitously expressed across multiple organ systems, exerts neuroprotective effects by maintaining intracellular homeostasis and mitigating neuronal damage triggered by oxidative stress, inflammatory cascades, apoptotic signaling, and ischemic insults. Furthermore, GLP-1R activity is modulated by gut microbiota composition and short-chain fatty acid abundance, implicating the gut–brain axis in its regulatory influence on neurological function. This review systematically examines the pathophysiological mechanisms underlying CCH and highlights the therapeutic potential of GLP-1R activation. Specifically, GLP-1R-targeted interventions attenuate hypoperfusion-induced damage through pleiotropic pathways and gut–brain crosstalk, thereby offering novel perspectives for advancing both fundamental research and clinical management of neurocognitive disorders.