| Yazarlar |
Shereen G Ghosh
|
|
Kerstin Becker
|
|
He Huang
|
|
Tracy Dixon-Salazar
|
|
Guoliang Chai
|
|
Vincenzo Salpietro
|
|
Lihadh Al-Gazali
|
|
Quinten Waisfisz
|
|
Haicui Wang
|
|
Keith K Vaux
|
|
Valentina Stanley
|
|
Andreea Manole
|
Dr. Öğr. Üyesi Uğur AKPULAT
Kastamonu Üniversitesi, Türkiye |
|
Marjan M Weiss
|
|
Stephanie Efthymiou
|
|
Michael G Hanna
|
|
Carlo Minetti
|
|
Pasquale Striano
|
|
Livia Pisciotta
|
|
Grandis Elisa De
|
|
Janine Altmüller
|
|
Peter Nürnberg
|
|
Holger Thiele
|
|
Uluç Yiş
Dokuz Eylül Üniversitesi, Türkiye |
|
Tuncay Derya Okur
|
|
Ayse Ipek Polat
|
|
Nafise Amiri
|
|
Mohammad Doosti
|
|
Ehsan Ghayoor Karimani
|
|
Mehran B Toosi
|
|
Gabriel Haddad
|
|
Mert Karakaya
|
|
Brunhilde Wirth
|
|
Hagen Johanna Van
|
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Nicole I Wolf
|
|
Reza Maroofian
|
|
Henry Houlden
|
|
Sebahattin Cirak
|
|
Joseph G Gleeson
|
| Özet |
| ADP-ribosylation, the addition of poly-ADP ribose (PAR) onto proteins, is a response signal to cellular challenges, such as excitotoxicity or oxidative stress. This process is catalyzed by a group of enzymes referred to as poly(ADP-ribose) polymerases (PARPs). Because the accumulation of proteins with this modification results in cell death, its negative regulation restores cellular homeostasis: a process mediated by poly-ADP ribose glycohydrolases (PARGs) and ADP-ribosylhydrolase proteins (ARHs). Using linkage analysis and exome or genome sequencing, we identified recessive inactivating mutations in ADPRHL2 in six families. Affected individuals exhibited a pediatric-onset neurodegenerative disorder with progressive brain atrophy, developmental regression, and seizures in association with periods of stress, such as infections. Loss of the Drosophila paralog Parg showed lethality in response to oxidative challenge that was rescued by human ADPRHL2, suggesting functional conservation. Pharmacological inhibition of PARP also rescued the phenotype, suggesting the possibility of postnatal treatment for this genetic condition. |
| Anahtar Kelimeler |
| ADP-ribosylation | ADPRHL2 | ARH3 | ataxia | epilepsy | neurodegeneration | neuropathy | oxidative stress | poly-ADP ribose | SUDEP |
| Makale Türü | Özgün Makale |
| Makale Alt Türü | SSCI, AHCI, SCI, SCI-Exp dergilerinde yayımlanan tam makale |
| Dergi Adı | AMERICAN JOURNAL OF HUMAN GENETICS |
| Dergi ISSN | 0002-9297 |
| Dergi Tarandığı Indeksler | SCI-Expanded |
| Makale Dili | İngilizce |
| Basım Tarihi | 09-2018 |
| Cilt No | 103 |
| Sayı | 3 |
| Sayfalar | 431 / 439 |
| Doi Numarası | 10.1016/j.ajhg.2018.07.010 |
| Makale Linki | https://linkinghub.elsevier.com/retrieve/pii/S0002929718302374 |
| Atıf Sayıları | |
| SCOPUS | 62 |
| Google Scholar | 84 |
