Adiponectin Signaling in Neurodegenerative Disorders

Adiponectin is an adipocyte-derived hormone that influences systemic energy homeostasis and exerts direct actions within the central nervous system. Circulating adiponectin crosses the blood–brain barrier via specific transport mechanisms or modulates barrier permeability to access key brain regions. Within neuronal and glial populations, adiponectin signals through two seven-transmembrane receptors, AdipoR1 and AdipoR2, activating downstream cascades such as AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor alpha (PPARα), p38 mitogen-activated protein kinase (p38MAPK) and SIRT1–PGC1α pathways. These molecular programmes converge on synaptic plasticity, neurogenesis and anti-inflammatory responses, mitigating oxidative stress and excitotoxicity. Dysregulation of adiponectin signalling has been implicated in the pathogenesis of Alzheimer’s disease, Parkinson’s disease and amyotrophic lateral sclerosis, where impaired insulin sensitivity, chronic neuroinflammation and mitochondrial dysfunction are prominent. Emerging evidence highlights adiponectin receptor agonists and peptide mimetics as potential therapeutic agents capable of restoring metabolic balance, promoting neuronal survival and slowing cognitive decline.

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Adiponectin Signaling in Neurodegenerative Disorders publication trend

The graph below shows the total number of articles in adiponectin signaling in neurodegenerative disorders across all publications each year (not limited to Nature Index journals).

Technical terms

Adiponectin: A hormone secreted by adipose tissue that regulates glucose and lipid metabolism and exerts neuroprotective effects in the CNS.

AdipoR1 and AdipoR2: Seven-transmembrane receptors for adiponectin expressed in neuronal and glial cells, mediating distinct intracellular pathways.

AMPK (AMP-activated protein kinase): A cellular energy sensor that, when activated by adiponectin, promotes mitochondrial biogenesis and anti-inflammatory responses.

Blood–brain barrier (BBB): A selective endothelial interface that regulates the passage of molecules between the circulation and the central nervous system.

Neuroinflammation: Activation of glial cells and release of pro-inflammatory mediators within the CNS, contributing to neuronal dysfunction.

Synaptic plasticity: The ability of synapses to strengthen or weaken over time, essential for learning, memory and neuronal adaptation.

Neurogenesis: The process by which new neurons are generated from neural stem or progenitor cells, particularly in the hippocampus.

References

1. Overview of a novel osmotin abolishes abnormal metabolic-associated adiponectin mechanism in Alzheimer’s disease: Peripheral and CNS insights. Ageing Research Reviews (2024).
2. Pharmacological and physiological roles of adipokines and myokines in metabolic-related dementia. Biomedicine & Pharmacotherapy (2023).
3. The Role of Adipokines in the Pathologies of the Central Nervous System. International Journal of Molecular Sciences (2023).
4. Secret talk between adipose tissue and central nervous system via secreted factors—an emerging frontier in the neurodegenerative research. Journal of Neuroinflammation (2016).
5. Adiponectin and Cognitive Decline. International Journal of Molecular Sciences (2020).
6. Adiponectin is Protective against Oxidative Stress Induced Cytotoxicity in Amyloid-Beta Neurotoxicity. PLOS ONE (2012).
7. Adiponectin Stimulates Proliferation of Adult Hippocampal Neural Stem/Progenitor Cells through Activation of p38 Mitogen-activated Protein Kinase (p38MAPK)/Glycogen Synthase Kinase 3β (GSK-3β)/β-Catenin Signaling Cascade*. Journal of Biological Chemistry (2011).
8. Adiponectin Protects against Glutamate‐Induced Excitotoxicity via Activating SIRT1‐Dependent PGC‐1α Expression in HT22 Hippocampal Neurons. Oxidative Medicine and Cellular Longevity (2016).