| First Author | Bi HR | Year | 2021 |
| Journal | CNS Neurosci Ther | Volume | 27 |
| Issue | 2 | Pages | 174-185 |
| PubMed ID | 32961023 | Mgi Jnum | J:326593 |
| Mgi Id | MGI:7314892 | Doi | 10.1111/cns.13454 |
| Citation | Bi HR, et al. (2021) Neuron-specific deletion of presenilin enhancer2 causes progressive astrogliosis and age-related neurodegeneration in the cortex independent of the Notch signaling. CNS Neurosci Ther 27(2):174-185 |
| abstractText | INTRODUCTION: Presenilin enhancer2 (Pen-2) is an essential subunit of gamma-secretase, which is a key protease responsible for the cleavage of amyloid precursor protein (APP) and Notch. Mutations on Pen-2 cause familial Alzheimer disease (AD). However, it remains unknown whether Pen-2 regulates neuronal survival and neuroinflammation in the adult brain. METHODS: Forebrain neuron-specific Pen-2 conditional knockout (Pen-2 cKO) mice were generated for this study. Pen-2 cKO mice expressing Notch1 intracellular domain (NICD) conditionally in cortical neurons were also generated. RESULTS: Loss of Pen-2 causes astrogliosis followed by age-dependent cortical atrophy and neuronal loss. Loss of Pen-2 results in microgliosis and enhanced inflammatory responses in the cortex. Expression of NICD in Pen-2 cKO cortices ameliorates neither neurodegeneration nor neuroinflammation. CONCLUSIONS: Pen-2 is required for neuronal survival in the adult cerebral cortex. The Notch signaling may not be involved in neurodegeneration caused by loss of Pen-2. |
