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<p>Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are emerging as potential neuroprotective drugs in neurodegenerative diseases. These drugs were initially developed to manage type 2 diabetes (T2D) and obesity. In addition to GLP-1RAs having an impact on metabolic pathways, growing evidences suggests that GLP-1RAs also positively regulate mitochondrial homeostasis in several neuronal cell types such as hippocampal, cortical, dopaminergic and hypothalamic. These modulatory effect of activated GLP-1R in the brain might be playing a crucial role which ultimately leads to neuronal cell survival, synaptic function, and improve in neuroinflammation in case neurodegenerative diseases. Although GLP-1RAs show promise in enhancing mitochondrial health, major gaps remain in understanding cell-type-specific responses, sex- and age-related differences, and the precise mechanistic links between GLP-1 signaling in mitochondrial biogenesis, dynamics, and mitophagy. This review summarises current understanding of GLP-1RA-induced mitochondrial regulation in the central nervous system. It also highlights key knowledge gaps, including cell type specificity and the lack of mechanistic as well as translational studies linking GLP-1RA signalling to mitochondrial regulation in the human CNS, which must be addressed to harness their full neuroprotective potential.</p>

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GLP-1 and the brain’s powerhouse: a new perspective on the role of mitochondria in neuroprotection

  • 期刊论文

  • 发表日期：

    2026年4月1日

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  • Tiasha Dasgupta,
  • Hitesh Bhayani,
  • Krishnarup Ghoshdastidar,
  • Kasinath Viswanathan,
  • Mukul Jain

摘要

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are emerging as potential neuroprotective drugs in neurodegenerative diseases. These drugs were initially developed to manage type 2 diabetes (T2D) and obesity. In addition to GLP-1RAs having an impact on metabolic pathways, growing evidences suggests that GLP-1RAs also positively regulate mitochondrial homeostasis in several neuronal cell types such as hippocampal, cortical, dopaminergic and hypothalamic. These modulatory effect of activated GLP-1R in the brain might be playing a crucial role which ultimately leads to neuronal cell survival, synaptic function, and improve in neuroinflammation in case neurodegenerative diseases. Although GLP-1RAs show promise in enhancing mitochondrial health, major gaps remain in understanding cell-type-specific responses, sex- and age-related differences, and the precise mechanistic links between GLP-1 signaling in mitochondrial biogenesis, dynamics, and mitophagy. This review summarises current understanding of GLP-1RA-induced mitochondrial regulation in the central nervous system. It also highlights key knowledge gaps, including cell type specificity and the lack of mechanistic as well as translational studies linking GLP-1RA signalling to mitochondrial regulation in the human CNS, which must be addressed to harness their full neuroprotective potential.