The molecular processes underlying neurodegenerative diseases (such as Alzheimer's Disease
- AD) remain poorly understood. There is also an imperative need for disease-modifying therapies
in AD since the present treatments, acetylcholinesterase inhibitors and NMDA antagonists, do not halt
its progression. AD and other dementias present unique pathological features such as that of microtubule
associated protein tau metabolic regulation. Tau has numerous binding partners, including signaling
molecules, cytoskeletal elements and lipids, which suggests that it is a multifunctional protein. AD
has also been associated with severe loss of cholinergic markers in the brain and such loss may be due
to the toxic interaction of tau with cholinergic muscarinic receptors. By using specific antagonists of
muscarinic receptors it was found in vitro that extracellular tau binds to M1 and M3 receptors and
which the increase of intracellular calcium found in neuronal cells upon tau-binding. However, so far,
the significance of tau signaling through muscarinic receptor in vivo in tauopathic models remains uncertain.
The data reviewed in the present paper highlight the significant effect of M1 receptor/tau interaction
in exacerbating tauopathy related pathological features and suggest that selective M1 agonists
may serve as a prototype for future therapeutic development toward modification of currently intractable
neurodegenerative diseases, such as tauopathies.