Ontology highlight
ABSTRACT: Introduction
Presenilin enhancer2 (Pen-2) is an essential subunit of ?-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.
SUBMITTER: Bi HR
PROVIDER: S-EPMC7816208 | biostudies-literature | 2021 Feb
REPOSITORIES: biostudies-literature
Bi Hui-Ru HR Zhou Cui-Hua CH Zhang Yi-Zhi YZ Cai Xu-Dong XD Ji Mu-Huo MH Yang Jian-Jun JJ Chen Gui-Quan GQ Hu Yi-Min YM
CNS neuroscience & therapeutics 20200922 2
<h4>Introduction</h4>Presenilin enhancer2 (Pen-2) is an essential subunit of γ-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.<h4>Methods</h4>Forebrain neuron-specific Pen-2 conditional knockout (Pen-2 cKO) mice were generated for this study. Pen-2 cKO mice expressing ...[more]