Serotonergic Regulation in Alzheimer's Disease
Lyudmila P Dolgacheva1, Valery P Zinchenko1, Alexander D Nadeev1
1Federal Research Center "Pushchino Scientific Center for Biological Research of the Russian Academy of Sciences", Institute of Cell Biophysics of the Russian Academy of Sciences, Pushchino 142290, Russia.
International Journal of Molecular Sciences
|June 13, 2025
Summary
Serotonin (5-HT) dysfunction contributes to Alzheimer's disease (AD) by affecting brain development and mitochondrial health. Targeting the 5-HT system offers potential therapeutic strategies for AD prevention and treatment.
Area of Science:
- Neuroscience
- Pharmacology
- Pathology
Background:
- Serotonin (5-HT) regulates vascular tone and angiogenesis, and its system is implicated in Alzheimer's disease (AD) pathogenesis.
- Dysfunction of the 5-HT system is linked to AD development, depression, and stress, with potential therapeutic targets in 5-HT receptors.
- Circadian rhythm disruption exacerbates AD by impairing amyloid-beta (Aβ) plaque clearance and modulating disease progression.
Purpose of the Study:
- To review the involvement of the serotonin (5-HT) system in Alzheimer's disease (AD) pathology.
- To explore the role of 5-HT in brain development, neuronal plasticity, and neuroprotection.
- To discuss therapeutic strategies targeting the 5-HT system for AD prevention and treatment.
Main Methods:
- Literature review of studies on serotonin, Alzheimer's disease, and related factors.
- Analysis of the impact of 5-HT on Aβ plaque clearance, circadian rhythms, and mitochondrial function.
- Examination of the neurodevelopmental and neuroregenerative roles of 5-HT.
Main Results:
- Serotonin (5-HT) system damage contributes to AD; 5-HT receptor subtypes are potential therapeutic targets.
- Interaction of amyloid-beta oligomers (AβO) with mitochondria triggers AD neurodegeneration.
- 5-HT improves mitochondrial quality and aids brain area restoration after injury or stress, relevant to AD.
Conclusions:
- The serotonin (5-HT) system plays a critical role in brain development, plasticity, and neuroprotection, influencing Alzheimer's disease progression.
- Targeting 5-HT receptors and promoting a healthy lifestyle may offer promising avenues for AD prevention and treatment.
- Restoring 5-HT function can improve mitochondrial health and aid recovery from neurological damage, counteracting AD-related neurodegeneration.
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