Neuroprotective Effects of Phosphodiesterase Inhibitors on Sestrin-2 (SESN2) Expression and Autophagy in Alzheimer's Disease Model.

Objective: Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline and the accumulation of amyloid-beta (Aβ) peptides. The neuroprotective protein sestrin-2 (SESN2) has been implicated in the cellular response to oxidative stress and autophagy, processes that are disrupted in AD. This study explores the effects of phosphodiesterase inhibitors (PDEIs) roflumilast (RF), rolipram (ROL), and tadalafil (TAD) on SESN2 expression and autophagy in Aβ25-35-treated hippocampal neuron (HT-22) cell cultures.

Indinavir inhibits the expression of cytoplasmic aromatase and nuclear SREBP in the hippocampus of reperfusion injury-induced ischemic rats.

Ischemic brain injury due to insults, such as stroke, is a leading cause of severe neurological and neurobehavioral deficits and death. Neurodegeneration can be prevented by local aromatase expression, and estrogen synthesis can be neuroprotective in ischemia/reperfusion. Therefore, aromatase, the enzyme that transforms androgens to estrogens, may be a potential target for the study of reperfusion injury after brain ischemia.