Air pollution amyloidogenesis is attenuated by the gamma-secretase modulator GSM-15606.
Alzheimers Dement
; 2024 Aug 12.
Article
em En
| MEDLINE
| ID: mdl-39132765
ABSTRACT
INTRODUCTION:
Chronic air pollution (AirPoll) is associated with accelerated cognitive decline and risk of Alzheimer's disease (AD). Correspondingly, wild-type and AD-transgenic rodents exposed to AirPoll have increased amyloid peptides and behavioral impairments.METHODS:
We examined the γ-secretase modulator GSM-15606 for potential AirPoll protection by its attenuating of amyloid beta (Aß)42 peptide production. Male and female wild-type mice were fed GSM-15606 during an 8-week inhalation exposure to AirPoll subfractions, ambient nanoparticulate matter (nPM), and diesel exhaust particles (DEP).RESULTS:
GSM-15606 decreased Aß42 during nPM and DEP exposure without changing beta- or gamma-secretase activity or BACE1 and PS1 protein levels. DEP increased lateral ventricle volume by 25%.DISCUSSION:
These enzyme responses are relevant to AD drug treatments, as well as to the physiological functions of the Aß42 peptide. GSM-15606 attenuation of Aß42 may benefit human exposure to AirPoll. HIGHLIGHTS Gamma-secretase modulator (GSM-15606) attenuates the amyloidogenic amyloid beta (Aß)42 peptide during exposure to air pollution, which may be a mechanism by which air pollution increases Alzheimer's disease (AD) risk. AD drug treatments may also consider Aß homeostasis among the chronic effects of GSM-15606 and other amyloid reduction treatments on secretase enzymes.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Revista:
Alzheimers Dement
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Estados Unidos
País de publicação:
Estados Unidos