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Therapeutic potential of acetyl-DL-leucine and its L-enantiomer in posterior fossa syndrome: Mechanistic insights
P. Vlček, J. Horáček, M. Grünerová-Lippertová, M. Brunovský
Language English Country England, Great Britain
Document type Journal Article, Review
- MeSH
- Infratentorial Neoplasms * surgery MeSH
- Leucine * analogs & derivatives therapeutic use pharmacology MeSH
- Humans MeSH
- Neuroprotective Agents * pharmacology therapeutic use MeSH
- Postoperative Complications * drug therapy MeSH
- Syndrome MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
Posterior fossa syndrome (PFS) is a serious postoperative complication that primarily affects children following resection of posterior fossa tumors. Although its complex pathophysiology, involving disruption of cerebellar structures and the dentato-thalamo-cortical pathway, is increasingly being elucidated, effective treatments remain limited. This perspective explores acetyl-DL-leucine (ADLL) and its active L-enantiomer, N-acetyl-L-leucine (NALL), as promising therapeutic candidates for PFS. Emerging mechanistic, preclinical, and clinical evidence suggests that both compounds might alleviate PFS symptoms through neuroprotective and neurorestorative mechanisms, including neuronal membrane stabilization, metabolic enhancement, antioxidant and anti-inflammatory effects, and dopaminergic modulation. NALL, which has greater neurotherapeutic potential than ADLL, might particularly support recovery through its multimodal effects on neuronal function, thereby enhancing perioperative resilience. Further translational research into these acetylated leucine analogues is warranted.
References provided by Crossref.org
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- $a Vlček, Přemysl $u Department of Psychiatry and Medical Psychology, Third Faculty of Medicine, Charles University, Prague, Czech Republic; Department of Rehabilitation, Third Faculty of Medicine, Charles University, Prague, Czech Republic; National Institute of Mental Health, Klecany, Czech Republic. Electronic address: premysl.vlcek@lf3.cuni.cz
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- $a Posterior fossa syndrome (PFS) is a serious postoperative complication that primarily affects children following resection of posterior fossa tumors. Although its complex pathophysiology, involving disruption of cerebellar structures and the dentato-thalamo-cortical pathway, is increasingly being elucidated, effective treatments remain limited. This perspective explores acetyl-DL-leucine (ADLL) and its active L-enantiomer, N-acetyl-L-leucine (NALL), as promising therapeutic candidates for PFS. Emerging mechanistic, preclinical, and clinical evidence suggests that both compounds might alleviate PFS symptoms through neuroprotective and neurorestorative mechanisms, including neuronal membrane stabilization, metabolic enhancement, antioxidant and anti-inflammatory effects, and dopaminergic modulation. NALL, which has greater neurotherapeutic potential than ADLL, might particularly support recovery through its multimodal effects on neuronal function, thereby enhancing perioperative resilience. Further translational research into these acetylated leucine analogues is warranted.
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