Greig_2005_Proc.Natl.Acad.Sci.U.S.A_102_17213

Reference

Title : Selective butyrylcholinesterase inhibition elevates brain acetylcholine, augments learning and lowers Alzheimer beta-amyloid peptide in rodent - Greig_2005_Proc.Natl.Acad.Sci.U.S.A_102_17213
Author(s) : Greig NH , Utsuki T , Ingram DK , Wang Y , Pepeu G , Scali C , Yu QS , Mamczarz J , Holloway HW , Giordano T , Chen D , Furukawa K , Sambamurti K , Brossi A , Lahiri DK
Ref : Proc Natl Acad Sci U S A , 102 :17213 , 2005
Abstract :

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 (maze navigation) of aged rats. In cultured human SK-N-SH neuroblastoma cells, intra- and extracellular beta-amyloid precursor protein, and secreted beta-amyloid peptide levels were reduced without affecting cell viability. Treatment of transgenic mice that overexpressed human mutant amyloid precursor protein also resulted in lower beta-amyloid peptide brain levels than controls. Selective, reversible inhibition of brain BChE may represent a treatment for Alzheimer's disease, improving cognition and modulating neuropathological markers of the disease.

PubMedSearch : Greig_2005_Proc.Natl.Acad.Sci.U.S.A_102_17213
PubMedID: 16275899

Related information

Inhibitor Cymserine

Citations formats

Greig NH, Utsuki T, Ingram DK, Wang Y, Pepeu G, Scali C, Yu QS, Mamczarz J, Holloway HW, Giordano T, Chen D, Furukawa K, Sambamurti K, Brossi A, Lahiri DK (2005)
Selective butyrylcholinesterase inhibition elevates brain acetylcholine, augments learning and lowers Alzheimer beta-amyloid peptide in rodent
Proc Natl Acad Sci U S A 102 :17213

Greig NH, Utsuki T, Ingram DK, Wang Y, Pepeu G, Scali C, Yu QS, Mamczarz J, Holloway HW, Giordano T, Chen D, Furukawa K, Sambamurti K, Brossi A, Lahiri DK (2005)
Proc Natl Acad Sci U S A 102 :17213