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Drugs and targets


The molecular pathogenesis of Alzheimer's disease is unclear. But, there are several reasonable hypothesis and targets.


A-beta:The amyloid deposition is one of important pathological features of Alzheimer's disease. The senile plaques is formed mainly by A-beta.


A-beta is produced by amyloid precursor protein metabolism, so, several enzymes in the process of amyloid precursor protein metabolism all are the targets.


1)Alpha-secretase : Alpha-secretase is the first enzyme in the unamyloid pathway of the amyloid precursor protein. Alpha-secretase activator can effectively reduce the amount of A-beta.


2)Beta-secretase: Beta-secretase is the first enzyme in the unamyloid pathway. So, beta-secretase is one of important target.


3) Gamma-secretase: Gamma-secretase enzyme is directly related to the A-beta generation.


There are several pilot compound has entered into phase III clinical stage currently.


Tau protein: The neurofibrillary tangles are an important pathological feature of Alzheimer's disease. Neurofibrillary tangles are composed by the hyperphosphorylated tau protein. The study includes inhibiting tau phosphorylation、Promoting the dephosphorylation of tau protein and so on. 


Cholinesterase: The ability of learning and memory significantly decline in AD patients is one of important Symptoms. Pathological study confirmed that cholinergic neurons degenerate in AD patients. Central cholinergic system is closely related to learning and memory ability.


1) Cholinesterase inhibitors: donepezil hydrochloride RDT, donepezil hydrochloride, tacrine, galantamine, rivastignine tartrate.


2) Cholinergic receptor agonists: xanomeline, milameline

Glutamate receptors: Glutamate is the main excitatory neurotransmitter in the central nervous system. Glutamate receptor abnormalities may increase the A-beta in central nervous system.


Drugs: Characteristics


Drugs for the treatment of Alzheimer's disease on the market are to alleviate the symptoms of Alzheimer's disease. There are no drugs can be used to cure this disease.

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