2021年12月
Reversibility of motor dysfunction in the rat model of NGLY1 deficiency
Molecular Brain
- ,
- ,
- ,
- ,
- ,
- 巻
- 14
- 号
- 1
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1186/s13041-021-00806-6
- 出版者・発行元
- Springer Science and Business Media LLC
<title>Abstract</title><italic>N-</italic>glycanase 1 (NGLY1) deficiency is a rare inherited disorder characterized by developmental delay, hypolacrima or alacrima, seizure, intellectual disability, motor deficits, and other neurological symptoms. The underlying mechanisms of the NGLY1 phenotype are poorly understood, and no effective therapy is currently available. Similar to human patients, the rat model of NGLY1 deficiency, <italic>Ngly1</italic>−/−, shows developmental delay, movement disorder, somatosensory impairment, scoliosis, and learning disability. Here we show that single intracerebroventricular administration of AAV9 expressing human NGLY1 cDNA (AAV9-hNGLY1) to <italic>Ngly1</italic>−/− rats during the weaning period restored NGLY1 expression in the brain and spinal cord, concomitant with increased enzymatic activity of NGLY1 in the brain. hNGLY1 protein expressed by AAV9 was found predominantly in mature neurons, but not in glial cells, of <italic>Ngly1</italic>−/− rats. Strikingly, intracerebroventricular administration of AAV9-hNGLY1 normalized the motor phenotypes of <italic>Ngly1</italic>−/− rats assessed by the rota-rod test and gait analysis. The reversibility of motor deficits in <italic>Ngly1</italic>−/− rats by central nervous system (CNS)-restricted gene delivery suggests that the CNS is the primary therapeutic target organs for NGLY1 deficiency, and that the <italic>Ngly1</italic>−/− rat model may be useful for evaluating therapeutic treatments in pre-clinical studies.
- リンク情報
- ID情報
-
- DOI : 10.1186/s13041-021-00806-6
- eISSN : 1756-6606