Inhibition of phosphodiesterase: A novel therapeutic target for the treatment of mild cognitive impairment and Alzheimer's disease.

Alzheimer's disease (AD) is the most common form of dementia and is ranked as the 6th leading cause of death in the US. The prevalence of AD and dementia is steadily increasing and expected cases in USA is 14.8 million by 2050.

Therapeutic Interventions of Gut-Brain Axis as Novel Strategies for Treatment of Alcohol Use Disorder Associated Cognitive and Mood Dysfunction.

Alcohol use disorders (AUD) is characterized by persistent or intermittent alcohol cravings and compulsive drinking. The functional changes in the central nervous system (CNS) after alcohol consumption are alcohol-associated cognitive impairment and mood disorders, which are major health issues reported in AUDs. Studies have shown that transferring the intestinal microbiota from AUDs patients to germ-free animals causes learning and memory dysfunction, depression and anxiety-like behavior, indicating the vital role of intestinal microbiota in development of neuropsychiatric disorders in AUD.

Phosphodiesterase-4D Knockdown in the Prefrontal Cortex Alleviates Memory Deficits and Synaptic Failure in Mouse Model of Alzheimer's Disease.

Phosphodiesterase 4 (PDE4)-dependent cAMP signaling plays a crucial role in cognitive impairment associated with Alzheimer's disease (AD). However, whether inhibition of PDE4 subtypes or their splice variants in the prefrontal cortex positively regulates synaptic plasticity and antioxidative stress, and reverses β-amyloid 1-42 (Aβ1-42, Aβ42)-induced cognitive impairment still need to be clarified. The present study determined whether and how PDE4D knockdown by microinjection of lenti-PDE4D-miRNA into the prefrontal cortex reversed Aβ1-42-induced cognitive impairment in behavioral, neurochemical, and molecular biology assays.