Selective butyrylcholinesterase inhibition elevates brain acetylcholine, augments learning and lowers Alzheimer β-amyloid peptide in rodent

Like acetylcholinesterase, butyrylcholinesterase (BChE) inactivates the neurotransmitter acetylcholine (ACh) and is hence a viable therapeutic target in Alzheimer's disease, which is characterized by a cholinergic deficit. Potent, reversible, and brain-targeted BChE inhibitors (cymserine analogs) were developed based on binding domain structures to help elucidate the role of this enzyme in the central nervous system. In rats, cymserine analogs caused long-term inhibition of brain BChE and elevated extracellular ACh levels, without inhibitory effects on acetylcholinesterase. In rat brain slices, selective BChE inhibition augmented long-term potentiation. These compounds also improved the cognitive performance…

• AA
  Alzheimer's Association

  Award: AG18379
• NI
  National Institutes of Health

  Awards: AG18379, AG18884