We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Downregulating PTBP1 Fails to Convert Astrocytes into Hippocampal Neurons and to Alleviate Symptoms in Alzheimer’s Mouse Models.
- Authors
Tiantian Guo; Xinjia Pan; Guangtong Jiang; Denghong Zhang; Jinghui Qi; Lin Shao; Zhanxiang Wang; Huaxi Xu; Yingjun Zhao
- Abstract
Conversion of astroglia into functional neurons has been considered a promising therapeutic strategy for neurodegenerative diseases. Recent studies reported that downregulation of the RNA binding protein, polypyrimidine tract-binding protein 1 (PTBP1), converts astrocytes into neurons in situ in multiple mouse brain regions, consequently improving pathologic phenotypes associated with Parkinson's disease, RGC loss, and aging. Here, we demonstrate that PTBP1 downregulation using an astrocyte-specific AAV-mediated shRNA system fails to convert hippocampal astrocytes into neurons in both male and female wild-type (WT) and β-amyloid (5×FAD) and tau (PS19) Alzheimer's disease (AD) mouse models and fails to reverse synaptic/cognitive deficits and AD-associated pathology in male mice. Similarly, PTBP1 downregulation cannot convert astrocytes into neurons in the striatum and substantia nigra in both male and female WT mice. Together, our study suggests that cell fate conversion strategy for neurodegenerative disease therapy through manipulating one single gene, such as PTBP1, warrants more rigorous scrutiny.
- Subjects
ALZHEIMER'S disease; NEUROFIBRILLARY tangles; RNA-binding proteins; NEURONS; ASTROCYTES; LABORATORY mice
- Publication
Journal of Neuroscience, 2022, Vol 42, Issue 38, p7309
- ISSN
0270-6474
- Publication type
Article
- DOI
10.1523/JNEUROSCI.1060-22.2022