Oligomeric amyloid ß preferentially targets neuronal and not glial mitochondrial-encoded mRNAs.
Alzheimers Dement
; 14(6): 775-786, 2018 06.
Article
in En
| MEDLINE
| ID: mdl-29396107
ABSTRACT
INTRODUCTION:
Our laboratories have demonstrated that accumulation of oligomeric amyloid ß (OAß) in neurons is an essential step leading to OAß-mediated mitochondrial dysfunction.METHODS:
Alzheimer's disease (AD) and matching control hippocampal neurons, astrocytes, and microglia were isolated by laser-captured microdissection from the same subjects, followed by whole-transcriptome sequencing. Complementary in vitro work was performed in OAß-treated differentiated SH-SY5Y, followed by the use of a novel CoQ10 analogue for protection. This compound is believed to be effective both in suppressing reactive oxygen species and also functioning in mitochondrial electron transport.RESULTS:
We report decreases in the same mitochondrial-encoded mRNAs in Alzheimer's disease laser-captured CA1 neurons and in OAß-treated SH-SY5Y cells, but not in laser-captured microglia and astrocytes. Pretreatment with a novel CoQ10 analogue, protects neuronal mitochondria from OAß-induced mitochondrial changes.DISCUSSION:
Similarity of expression changes in neurons from Alzheimer's disease brain and neuronal cells treated with OAß, and the effect of a CoQ10 analogue on the latter, suggests a pretreatment option to prevent OAß toxicity, long before the damage is apparent.Key words
Full text:
1
Database:
MEDLINE
Main subject:
RNA, Messenger
/
Amyloid beta-Peptides
/
RNA, Mitochondrial
/
Neurons
Limits:
Aged
/
Female
/
Humans
/
Male
Language:
En
Journal:
Alzheimers Dement
Year:
2018
Type:
Article