The mechanisms of neurodegenerative processes and current pharmacotherapy of Alzheimer's disease.
An increasing number of studies suggest that current pharmacotherapy used in Alzheimer's disease (AD), in addition to having a symptomatic effect, also may interact with the ongoing neuropathological processes in the brain. The oldest hypothesis explain the cause of the AD is the "cholinergic hypothesis", which states, that AD begins as a deficiency in the production of acetylcholine (ACh). Interactions between the cholinergic and serotoninergic systems are believed to play a role in the mechanism underlying AD. The activation of NMDA receptors and increase in intracellular Ca(++) concentration play key role in the development of neurodegenerative processes. Potassium channels may also be involved in several other steps within the cascade that leads to neurodegeneration. In the development of AD a great role play an imbalance between anabolism and catabolism causes an accumulation of amyloid beta-peptide (Abeta), which is a proposed trigger of the onset of AD. There are various therapeutic strategies in current pharmacotherapy of AD. Major group is inhibitors of acetylcholinesterase--donepezil, galantamine, physostigmine. The new effective treatments of AD are NMDA glutamate receptor antagonist-memantine and potassium channel openers such as retigabine. Experimental study suggest, that neprilisin, a rate-limiting peptidase, decreases neurodegeneration.
Gongadze
N
N
Antelava
N
N
Kezeli
T
T
Okudjava
M
M
Pachkoria
K
K
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000503:physiopathology*; D001921:Brain / Q000473:pathology* / Q000503:physiopathology*; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use*; D000077265:Donepezil; D006801:Humans; D007189:Indans / Q000627:therapeutic use*; D008875:Middle Aged; D009410:Nerve Degeneration / Q000473:pathology / Q000503:physiopathology; D010880:Piperidines / Q000627:therapeutic use*
D002800:Cholinesterase Inhibitors; D007189:Indans; D010880:Piperidines; D000077265:Donepezil