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Dangerous Liaisons: Tau Interaction with Muscarinic Receptors

Authors
  • Wysocka, Adrianna1
  • Palasz, Ewelina2
  • Steczkowska, Marta2
  • Niewiadomska, Grazyna1
  • 1 Nencki Institute of Experimental Biology, 02-093 Warsaw , (Poland)
  • 2 Mossakowski Medical Research Center, 02-093 Warsaw , (Poland)
Type
Published Article
Journal
Current Alzheimer Research
Publisher
Bentham Science Publishers
Publication Date
Mar 01, 2020
Volume
17
Issue
3
Pages
224–237
Identifiers
DOI: 10.2174/1567205017666200424134311
PMID: 32329686
PMCID: PMC7509759
Source
PubMed Central
Keywords
Disciplines
  • Current Alzheimer Research
License
Green

Abstract

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.

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