Leukotriene A4 hydrolase inhibition improves age related cognitive decline via modulation of synaptic function (Part 2/2)

Leukotrienes, a class of inflammatory bioactive lipids, are well studied
in the periphery but less is known of their importance in the brain. We
identified that the enzyme leukotriene A4 hydrolase (LTA4H) is expressed
in healthy mouse neurons, and inhibition of LTA4H in aged mice improves
hippocampal dependent memory. Single cell nuclear RNA sequencing of
hippocampal neurons after inhibition reveals major changes to genes
important for synaptic organization, structure, and activity. We propose
that LTA4H inhibition may act to improve cognition by directly inhibiting
the enzymatic activity in neurons leading to improved synaptic function.
Additionally, LTA4H plasma levels are increased in both aging and
Alzheimer’s disease and correlated with cognitive impairment. These
results identify a novel role for LTA4H in the brain and we propose that
LTA4H inhibition may be a promising therapeutic strategy to treat
cognitive decline in aging related diseases.