Long-term forced-use therapy after sensorimotor cortex lesions restores contralesional hand function and promotes its preference in Macaca mulatta.

Injury to one cerebral hemisphere can result in paresis of the contralesional hand and subsequent preference of the ipsilesional hand in daily activities. However, forced use therapy in humans can improve function of the contralesional paretic hand and increase its use in daily activities, although the ipsilesional hand may remain preferred for fine motor activities. Studies in monkeys have shown that minimal forced use of the contralesional hand, which was the preferred hand prior to brain injury, can produce remarkable recovery of function.

First Demonstration of PDE11A4 Target Engagement for Potential Treatment of Age-Related Memory Disorders.

PDE11A4 is a target of interest for the treatment of age-related memory disorders. A previous report from our laboratories described an amide series of potent, selective PDE11A4 inhibitors that was metabolically unstable. Investigation of heterocyclic amide isosteres for the labile amide moiety revealed distinct structure-activity relationships and identified several compounds with potency comparable to the amide series.

Structure-Activity Relationship of a Pyrrole Based Series of PfPKG Inhibitors as Anti-Malarials.

Controlling malaria requires new drugs against . The cGMP-dependent protein kinase (PfPKG) is a validated target whose inhibitors could block multiple steps of the parasite's life cycle. We defined the structure-activity relationship (SAR) of a pyrrole series for PfPKG inhibition.

First Optimization of Novel, Potent, Selective PDE11A4 Inhibitors for Age-Related Cognitive Decline.

Phosphodiesterase 11A4 (PDE11A4) is a dual-acting cyclic nucleotide hydrolase expressed in neurons in the CA1, subiculum, amygdalostriatal transition area and amygdalohippocampal area of the extended hippocampal formation. PDE11A4 is the only PDE enzyme to emanate solely from hippocampal formation, a key brain region for the formation of long-term memory. PDE11A4 expression increases in the hippocampal formation of both humans and rodents as they age.