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Fluoride-induced Neurodevelopmental Toxicity- AMPK as a Possible Target
Tejas Ahuja1, Farmiza Begum2, Fathima Beegum1
1Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, 576104, Karnataka, India.
CNS & Neurological Disorders Drug Targets
|February 25, 2025
Summary
Excess inorganic fluoride exposure, particularly sodium fluoride (NaF), harms developing brains by increasing oxidative stress. AMPK activation may offer a therapeutic target against fluoride-induced neurotoxicity.
Area of Science:
- Neuroscience
- Toxicology
- Biochemistry
Background:
- Inorganic fluoride is used in dentistry but excess intake is toxic.
- Sodium fluoride (NaF) exposure impacts the central nervous system, especially during development.
- NaF neurotoxicity is linked to oxidative stress, neuronal damage, and impaired cognitive functions.
Purpose of the Study:
- To review fluoride's role in neurodevelopment.
- To elucidate mechanisms of fluoride-induced neurotoxicity.
- To explore AMP-activated protein kinase (AMPK) as a potential therapeutic target.
Main Methods:
- Literature review of studies on fluoride neurotoxicity.
- Analysis of biochemical pathways involved in NaF toxicity.
- Investigation of natural compounds and signaling pathways for neuroprotection.
Main Results:
- NaF exposure induces oxidative stress, mitochondrial dysfunction, and neuronal cell death.
- Key pathways affected include those regulating receptors, autophagy, apoptosis, and energy metabolism.
- Increased oxidative stress is a primary mechanism in fluoride neurotoxicity.
Conclusions:
- Fluoride exposure poses significant risks to neurodevelopment.
- Understanding NaF toxicity mechanisms is crucial for developing interventions.
- AMPK presents a promising therapeutic target for mitigating fluoride-induced neurotoxicity.
