Muscarinic agonists reduce tau phosphorylation in non-neuronal cells via GSK-3β inhibition and in neurons
Research output: Contribution to journal › Journal article › Research › peer-review
Muscarinic agonists alter the metabolism of amyloid precursor protein, leading to an increase in α-secretase cleavage and a decreased production of amyloidogenic peptides; suggesting that these compounds might modify the Alzheimer's disease process. A second therapeutic target in AD is the accumulation of stably phosphorylated tau into neurofibrillary tangles; an early event correlating with cognitive impairment. Glycogen synthase kinase-3 (GSK-3β) phosphorylates tau and is inhibited via protein kinase C (PKC). As certain muscarinic receptors are linked to PKC, we examined the effect of a range of agonists on GSK-3β phosphorylation of tau. In neurons a non-specific muscarinic agonist, carbachol, reduced tau phosphorylation. In non-neuronal cells expressing the m1 receptor a range of m1 agonists reduced transiently-expressed tau phosphorylation and altered its microtubule-binding properties. These findings link the two pathological process of AD - APP metabolism and tau phosphorylation - and suggest that muscarinic and other cholinergic compounds might have disease-modifying properties.
Original language | English |
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Journal | Journal of Neural Transmission |
Volume | 107 |
Issue number | 10 |
Pages (from-to) | 1201-1212 |
Number of pages | 12 |
ISSN | 0300-9564 |
DOIs | |
Publication status | Published - 2000 |
- Acetylcholine, Alzheimer's disease, Glycogen synthase kinase-3, Muscarinic receptor, Tau
Research areas
ID: 252063173