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, 2021 02.
Article
in En
| MEDLINE
| ID: mdl-32961023
ABSTRACT
INTRODUCTION:
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.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.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Aging
/
Cerebral Cortex
/
Receptors, Notch
/
Amyloid Precursor Protein Secretases
/
Gliosis
/
Neurons
Type of study:
Etiology_studies
Limits:
Animals
Language:
En
Journal:
CNS Neurosci Ther
Journal subject:
NEUROLOGIA
/
TERAPEUTICA
Year:
2021
Document type:
Article
Affiliation country:
China