Редактирование: WFS1

Wolframin

==Publications==

{{medline-entry
|title=Knockdown of wfs1, a fly homolog of Wolfram syndrome 1, in the nervous system increases susceptibility to age- and stress-induced neuronal dysfunction and degeneration in Drosophila.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/29357349
|abstract=Wolfram syndrome (WS), caused by loss-of-function mutations in the Wolfram syndrome 1 gene ([[WFS1]]), is characterized by juvenile-onset diabetes mellitus, bilateral optic atrophy, and a wide spectrum of neurological and psychiatric manifestations. [[WFS1]] encodes an endoplasmic reticulum (ER)-resident transmembrane protein, and mutations in this gene lead to pancreatic β-cell death induced by high levels of ER stress. However, the mechanisms underlying neurodegeneration caused by [[WFS1]] deficiency remain elusive. Here, we investigated the role of [[WFS1]] in the maintenance of neuronal integrity in vivo by knocking down the expression of wfs1, the Drosophila homolog of [[WFS1]], in the central nervous system. Neuronal knockdown of wfs1 caused age-dependent behavioral deficits and neurodegeneration in the fly brain. Knockdown of wfs1 in neurons and glial cells resulted in premature death and significantly exacerbated behavioral deficits in flies, suggesting that wfs1 has important functions in both cell types. Although wfs1 knockdown alone did not promote ER stress, it increased the susceptibility to oxidative stress-, excitotoxicity- or tauopathy-induced behavioral deficits, and neurodegeneration. The glutamate release inhibitor riluzole significantly suppressed premature death phenotypes induced by neuronal and glial knockdown of wfs1. This study highlights the protective role of wfs1 against age-associated neurodegeneration and furthers our understanding of potential disease-modifying factors that determine susceptibility and resilience to age-associated neurodegenerative diseases.
|mesh-terms=* Aging
* Animals
* Animals, Genetically Modified
* Cells, Cultured
* Drosophila melanogaster
* Gene Knockdown Techniques
* Genetic Predisposition to Disease
* Humans
* Membrane Proteins
* Mental Disorders
* Nerve Degeneration
* Nervous System
* Neurons
* Sequence Homology
* Stress, Psychological
* Wolfram Syndrome

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5794194
}}
{{medline-entry
|title=A nonsynonymous mutation in the [[WFS1]] gene in a Finnish family with age-related hearing impairment.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/28974383
|abstract=Wolfram syndrome (WS) is caused by recessive mutations in the Wolfram syndrome 1 ([[WFS1]]) gene. Sensorineural hearing impairment (HI) is a frequent feature in WS and, furthermore, certain mutations in [[WFS1]] cause nonsyndromic dominantly inherited low-frequency sensorineural HI. These two phenotypes are clinically distinct indicating that [[WFS1]] is a reasonable candidate for genetic studies in patients with other phenotypes of HI. Here we have investigated, whether the variation in [[WFS1]] has a pathogenic role in age-related hearing impairment (ARHI). [[WFS1]] gene was investigated in a population sample of 518 Finnish adults born in 1938-1949 and representing variable hearing phenotypes. Identified variants were evaluated with respect to pathogenic potential. A rare mutation predicted to be pathogenic was found in a family with many members with impaired hearing. Twenty members were recruited to a segregation study and a detailed clinical examination. Heterozygous p.Tyr528His variant segregated completely with late-onset HI in which hearing deteriorated first at high frequencies and progressed to mid and low frequencies later in life. We report the first mutation in the [[WFS1]] gene causing late-onset HI with audiogram configurations typical for ARHI. Monogenic forms of ARHI are rare and our results add [[WFS1]] to the short list of such genes.
|mesh-terms=* Acoustic Stimulation
* Adolescent
* Adult
* Age Factors
* Age of Onset
* Aged
* Aged, 80 and over
* Aging
* Audiometry, Pure-Tone
* DNA Mutational Analysis
* Female
* Finland
* Genetic Predisposition to Disease
* Hearing
* Hearing Loss, Sensorineural
* Heterozygote
* Humans
* Male
* Membrane Proteins
* Middle Aged
* Mutation
* Pedigree
* Phenotype
* Presbycusis
* Young Adult
|keywords=* Age-related hearing impairment
* High-frequency hearing impairment
* Presbyacusis
* Wolfram syndrome
|full-text-url=https://sci-hub.do/10.1016/j.heares.2017.09.013
}}