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Chemical chaperone 4-phenylbutylate reduces mutant protein accumulation in the endoplasmic reticulum of arginine vasopressin neurons in a mouse model for familial neurohypophysial diabetes insipidus.
- Source :
-
Neuroscience letters [Neurosci Lett] 2018 Aug 24; Vol. 682, pp. 50-55. Date of Electronic Publication: 2018 Jun 07. - Publication Year :
- 2018
-
Abstract
- Familial neurohypophysial diabetes insipidus (FNDI), characterized by progressive polyuria and loss of arginine vasopressin (AVP) neurons, is an autosomal dominant disorder caused by AVP gene mutations. Our previous studies with FNDI model mice demonstrated that mutant proteins accumulated in the endoplasmic reticulum (ER) of AVP neurons. Here, we examined therapeutic effects of the chemical chaperone 4-phenylbutylate (4-PBA) in FNDI mice. Treatment with 4-PBA reduced mutant protein accumulation in the ER of FNDI mice and increased AVP release, leading to reduced urine volumes. Furthermore, AVP neuron loss under salt loading was attenuated by 4-PBA treatment. These data suggest that 4-PBA ameliorated mutant protein accumulation in the ER of AVP neurons and thereby prevented FNDI phenotype progression.<br /> (Copyright © 2018 Elsevier B.V. All rights reserved.)
- Subjects :
- Animals
Arginine Vasopressin genetics
Butylamines pharmacology
Diabetes Insipidus, Neurogenic drug therapy
Diabetes Insipidus, Neurogenic genetics
Disease Models, Animal
Endoplasmic Reticulum drug effects
Endoplasmic Reticulum genetics
Male
Mice
Mice, Inbred C57BL
Mutation drug effects
Neurons drug effects
Arginine Vasopressin metabolism
Butylamines therapeutic use
Diabetes Insipidus, Neurogenic metabolism
Endoplasmic Reticulum metabolism
Mutation physiology
Neurons metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1872-7972
- Volume :
- 682
- Database :
- MEDLINE
- Journal :
- Neuroscience letters
- Publication Type :
- Academic Journal
- Accession number :
- 29886132
- Full Text :
- https://doi.org/10.1016/j.neulet.2018.06.013