Dangerous Liaisons: Tau Interaction with Muscarinic Receptors.
Tau
cholinergic system
muscarinic receptors
neurodegenerative diseases
review
tauopathies.
Journal
Current Alzheimer research
ISSN: 1875-5828
Titre abrégé: Curr Alzheimer Res
Pays: United Arab Emirates
ID NLM: 101208441
Informations de publication
Date de publication:
2020
2020
Historique:
received:
05
04
2019
revised:
05
02
2020
accepted:
25
03
2020
pubmed:
25
4
2020
medline:
25
5
2021
entrez:
25
4
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 32329686
pii: CAR-EPUB-106091
doi: 10.2174/1567205017666200424134311
pmc: PMC7509759
doi:
Substances chimiques
MAPT protein, human
0
Receptor, Muscarinic M1
0
tau Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
224-237Informations de copyright
Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.
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