Pathological mechanism

Data

Name Protective effect of donepezil against beta amyloid neurotoxicity

Description

Hypothesis Neuronal Death Show Other

Extracelular pathological element beta Amyloid Show Other

Intracelular pathological element

Pathological action Is neurotoxic Show Other

Process

Process action

Transmitter(s)

Receptor(s)

Channel(s)

Pharmacological Agent Donepezil Show Other

Pharmacological Action Reduces Show Other

Brain region

Neuron

Cell model Cultured septal neurons Show Other

Cellular compartment

PubMed ID 15893738

Citation

AlzWeb Donepezil

Notes ... to examine the effect of donepezil on Abeta(1-40) induced neurotoxicity in primary cultures of rat septal neurons. Using immunohistochemical staining, almost all the neurons were found to be positive for vesicular acetylcholine transporter (VAChT) in these septal cultures. Septal neuronal cells were cultured for 7 days and then 15 micromol/L of Abeta(1-40) was added to the cell medium for 48 h. The cultured septal neurons were highly susceptible to Abeta toxicity, as shown by morphological examination and lactate dehydrogenase (LDH) assay. Donepezil concentration-dependently reduced the LDH efflux induced by Abeta(1-40), and the effect was significant at 100 nmol/L and above. Donepezil decreased both the negative peak at around 215 nm in the circular dichroism (CD) spectrum and the fluorescence intensity of thioflavin T in the presence of Abeta(1-40). These results suggest that donepezil exerts a neuroprotective effect by reducing the amount of the toxic form of Abeta fibrils in septal neuron cultures. These findings support the idea that the clinical efficacy of donepezil in AD is due to not only activation of cholinergic transmission, but also attenuation of neuronal damage. (Kimura et al., 2005)

Pathology Alzheimer Show Other

Stage

Question Exclude - Neurotoxicity

Claim