Non-Canonical Roles of Tau and Their Contribution to Synaptic Dysfunction
Open Access
- 20 September 2021
- journal article
- review article
- Published by MDPI AG in International Journal of Molecular Sciences
- Vol. 22 (18), 10145
- https://doi.org/10.3390/ijms221810145
Abstract
Tau plays a central role in a group of neurodegenerative disorders collectively named tauopathies. Despite the wide range of diverse symptoms at the onset and during the progression of the pathology, all tauopathies share two common hallmarks, namely the misfolding and aggregation of Tau protein and progressive synaptic dysfunctions. Tau aggregation correlates with cognitive decline and behavioural impairment. The mechanistic link between Tau misfolding and the synaptic dysfunction is still unknown, but this correlation is well established in the human brain and also in tauopathy mouse models. At the onset of the pathology, Tau undergoes post-translational modifications (PTMs) inducing the detachment from the cytoskeleton and its release in the cytoplasm as a soluble monomer. In this condition, the physiological enrichment in the axon is definitely disrupted, resulting in Tau relocalization in the cell soma and in dendrites. Subsequently, Tau aggregates into toxic oligomers and amyloidogenic forms that disrupt synaptic homeostasis and function, resulting in neuronal degeneration. The involvement of Tau in synaptic transmission alteration in tauopathies has been extensively reviewed. Here, we will focus on non-canonical Tau functions mediating synapse dysfunction.This publication has 156 references indexed in Scilit:
- Alzheimer brain-derived tau oligomers propagate pathology from endogenous tauScientific Reports, 2012
- Synaptic Released Zinc Promotes Tau Hyperphosphorylation by Inhibition of Protein Phosphatase 2A (PP2A)*Journal of Biological Chemistry, 2012
- The acetylation of tau inhibits its function and promotes pathological tau aggregationNature Communications, 2011
- Nuclear Tau, a Key Player in Neuronal DNA ProtectionJournal of Biological Chemistry, 2011
- Phosphorylation of Tau at Thr212, Thr231, and Ser262 Combined Causes NeurodegenerationJournal of Biological Chemistry, 2010
- Tau Potentiates Nerve Growth Factor-induced Mitogen-activated Protein Kinase Signaling and Neurite Initiation without a Requirement for Microtubule BindingOnline Journal of Public Health Informatics, 2010
- Changes in dendritic complexity and spine morphology in transgenic mice expressing human wild-type tauBrain Structure and Function, 2010
- Transmission and spreading of tauopathy in transgenic mouse brainNature, 2009
- Interaction of tau protein with the dynactin complexThe EMBO Journal, 2007
- An inhibitor of tau hyperphosphorylation prevents severe motor impairments in tau transgenic miceProceedings of the National Academy of Sciences of the United States of America, 2006