Targeting acetylcholinesterase to treat neurodegeneration


HOLZGRABE U., KAPKOVA P., Alptuzun V. , SCHEIBER J., KUGELMANN E.

EXPERT OPINION ON THERAPEUTIC TARGETS, cilt.11, ss.161-179, 2007 (SCI İndekslerine Giren Dergi)

  • Cilt numarası: 11 Konu: 2
  • Basım Tarihi: 2007
  • Doi Numarası: 10.1517/14728222.11.2.161
  • Dergi Adı: EXPERT OPINION ON THERAPEUTIC TARGETS
  • Sayfa Sayısı: ss.161-179

Özet

Neurodegenerative disorders, such as Alzheimer's disease, are often characterised by the degeneration of the cholinergic system. Thus, the aim of many treatment regimens is to support this system either by means of muscarinic agonists or by inhibitors of acetylcholinesterase (AChE), the latter being able to increase the concentration of acetylcholine. However, both pharmacological groups of drugs can only help in the beginning of the progressive disease. The finding that the occupation of the peripheral anionic site of AChE is able to stop the formation of the amyloid plaque led to the development of bivalent ligands that occupy both the active and the peripheral site. This dual action might be more beneficial for treatment of Alzheimer's disease than simple inhibition of the acetylcholine hydrolysis. Thus, the new bivalent ligands are the focus of this review.