Alleviation of Huntington pathology in mice by oral administration of food additive glyceryl tribenzoate.
Administration, Oral
Animals
Benzoates
/ administration & dosage
Benzoic Acid
/ pharmacology
Flavoring Agents
/ pharmacology
Food Preservatives
/ pharmacology
Gait Analysis
Hand Strength
Humans
Huntingtin Protein
/ drug effects
Huntington Disease
/ genetics
Mice
Mice, Transgenic
Motor Cortex
/ drug effects
Neostriatum
/ drug effects
Open Field Test
Rotarod Performance Test
Sodium Benzoate
/ metabolism
Gait analysis
Gliosis
Glyceryl tribenzoate
Huntingtin
Inflammation
Journal
Neurobiology of disease
ISSN: 1095-953X
Titre abrégé: Neurobiol Dis
Pays: United States
ID NLM: 9500169
Informations de publication
Date de publication:
06 2021
06 2021
Historique:
received:
12
11
2020
revised:
05
02
2021
accepted:
22
02
2021
pubmed:
27
2
2021
medline:
29
1
2022
entrez:
26
2
2021
Statut:
ppublish
Résumé
Huntington's disease (HD) is a neurodegenerative disorder characterized by accumulation of mutant huntingtin protein and significant loss of neurons in striatum and cortex. Along with motor difficulties, the HD patients also manifest anxiety and loss of cognition. Unfortunately, the clinically approved drugs only offer symptomatic relief and are not free from side effects. This study underlines the importance of glyceryl tribenzoate (GTB), an FDA-approved food flavoring ingredient, in alleviating HD pathology in transgenic N171-82Q mouse model. Oral administration of GTB significantly reduced mutant huntingtin level in striatum, motor cortex as well as hippocampus and increased the integrity of viable neurons. Furthermore, we found the presence of sodium benzoate (NaB), a FDA-approved drug for urea cycle disorders and glycine encephalopathy, in the brain of GTB-fed HD mice. Accordingly, NaB administration also markedly decreased huntingtin level in striatum and cortex. Glial activation is found to coincide with neuronal death in affected regions of HD brains. Interestingly, both GTB and NaB treatment suppressed activation of glial cells and inflammation in the brain. Finally, neuroprotective effect of GTB and NaB resulted in improved motor performance of HD mice. Collectively, these results suggest that GTB and NaB may be repurposed for HD.
Identifiants
pubmed: 33636386
pii: S0969-9961(21)00067-X
doi: 10.1016/j.nbd.2021.105318
pmc: PMC8026693
mid: NIHMS1677088
pii:
doi:
Substances chimiques
Benzoates
0
Flavoring Agents
0
Food Preservatives
0
HTT protein, human
0
Huntingtin Protein
0
glyceryl tribenzoate
0
Benzoic Acid
8SKN0B0MIM
Sodium Benzoate
OJ245FE5EU
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
105318Subventions
Organisme : BLRD VA
ID : IK6 BX004982
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG050431
Pays : United States
Organisme : NCCIH NIH HHS
ID : R01 AT010980
Pays : United States
Organisme : NINDS NIH HHS
ID : R21 NS108025
Pays : United States
Informations de copyright
Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.
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