We have located links that may give you full text access.
AMP-activated protein kinase activation in mediating phenylalanine-induced neurotoxicity in experimental models of phenylketonuria.
Journal of Inherited Metabolic Disease 2018 July
Phenylketonuria (PKU), one of the most prevalent autosomal recessive disorders of amino acid metabolism, is characterized by abnormal accumulation of phenylalanine, which can lead to intellectual disability. The main pathologic changes in the central nervous system of untreated phenylketonuric patients are reductions in the number of axons, dendrites, and synapses in the brain. Such alterations are thought to be mainly associated with the toxic effects caused by phenylalanine. However, the underlying molecular mechanisms have not been fully elucidated. The present study shows that a high concentration of phenylalanine remarkably inhibited neuronal neurite formation in vitro. Interestingly, AMP-activated protein kinase (AMPK), the energy status sensor, was activated in cultured cerebral cortical neurons upon phenylalanine treatment. Pretreatment with an AMPK inhibitor ameliorated the reduction of neurite formation caused by phenylalanine. In addition, the levels of the phosphorylated AMPK, the active form of AMPK, were significantly higher in the cerebral cortices of PKU mice with elevated phenylalanine levels in this brain region compared to those in wild-type control mice, whereas the density of dendritic spines on basal secondary dendrites of pyramidal neurons in prefrontal cortices of PKU mice was significantly decreased. Collectively, these findings indicate that AMPK activation is a key event in impaired neuronal dendritic development in PKU and consequently, a potential therapeutic target for developing neuroprotective strategies against phenylalanine-evoked brain injury in PKU.
Full text links
Related Resources
Trending Papers
Challenges in Septic Shock: From New Hemodynamics to Blood Purification Therapies.Journal of Personalized Medicine 2024 Februrary 4
Molecular Targets of Novel Therapeutics for Diabetic Kidney Disease: A New Era of Nephroprotection.International Journal of Molecular Sciences 2024 April 4
Perioperative echocardiographic strain analysis: what anesthesiologists should know.Canadian Journal of Anaesthesia 2024 April 11
The 'Ten Commandments' for the 2023 European Society of Cardiology guidelines for the management of endocarditis.European Heart Journal 2024 April 18
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app
All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.
By using this service, you agree to our terms of use and privacy policy.
Your Privacy Choices
You can now claim free CME credits for this literature searchClaim now
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app