Looking for novel functions of tau

2012 ◽  
Vol 40 (4) ◽  
pp. 653-655 ◽  
Author(s):  
Jesus Avila ◽  
Elena Gomez de Barreda ◽  
Almudena Fuster-Matanzo ◽  
Diana Simón ◽  
María Llorens-Martín ◽  
...  
Keyword(s):  
Cell Death ◽  
Neurodegenerative Disorders ◽  
Extracellular Space ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Tau Pathology ◽  
Microtubule Associated Proteins ◽  
Protein Tau ◽  
Adult Mice ◽  
Associated Proteins

The lack or excess of the protein tau can be deleterious for neurons. The absence of tau can result in retarded neurogenesis and neuronal differentiation, although adult mice deficient in tau are viable, probably because of the compensation of the loss of tau by other MAPs (microtubule-associated proteins). On the contrary, the overexpression of tau can be toxic for the cell. One way to reduce intracellular tau levels can be achieved by its secretion through microvesicles to the extracellular space. Furthermore, tau can be found in the extracellular space because of the neuronal cell death occurring in neurodegenerative disorders such as Alzheimer's disease. The presence of toxic extracellular tau could be the mechanism for the spreading of tau pathology in these neurodegenerative disorders.

scholarly journals Tau and DNA Damage in Neurodegeneration

2020 ◽  
Vol 10 (12) ◽  
pp. 946
Author(s):  
Luca Colnaghi ◽  
Diego Rondelli ◽  
Marco Muzi-Falconi ◽  
Sarah Sertic
Keyword(s):  
Dna Damage ◽  
Cell Death ◽  
Neurodegenerative Disorders ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Pathological Features ◽  
Synaptic Loss ◽  
Microtubule Binding ◽  
Protein Tau ◽  
Microtubule Associated Protein Tau

Neurodegenerative disorders are a family of incurable conditions. Among them, Alzheimer’s disease and tauopathies are the most common. Pathological features of these two disorders are synaptic loss, neuronal cell death and increased DNA damage. A key pathological protein for the onset and progression of the conditions is the protein tau, a microtubule-binding protein highly expressed in neurons and encoded by the MAPT (microtubule-associated protein tau) gene. Tau is predominantly a cytosolic protein that interacts with numerous other proteins and molecules. Recent findings, however, have highlighted new and unexpected roles for tau in the nucleus of neuronal cells. This review summarizes the functions of tau in the metabolism of DNA, describing them in the context of the disorders.

From tau phosphorylation to tau aggregation: what about neuronal death?

2010 ◽  
Vol 38 (4) ◽  
pp. 967-972 ◽  
Author(s):  
Luc Buée ◽  
Laëtitia Troquier ◽  
Sylvie Burnouf ◽  
Karim Belarbi ◽  
Anneke Van der Jeugd ◽  
...  
Keyword(s):  
Cell Death ◽  
Cognitive Impairment ◽  
Neurodegenerative Disorders ◽  
Neuronal Death ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Tau Phosphorylation ◽  
Tau Proteins ◽  
Phosphorylated Tau ◽  
Sequence Of Events

Tau pathology is characterized by intracellular aggregates of abnormally and hyperphosphorylated tau proteins. It is encountered in many neurodegenerative disorders, but also in aging. These neurodegenerative disorders are referred to as tauopathies. Comparative biochemistry of the tau aggregates shows that they differ in both tau isoform phosphorylation and content, which enables a molecular classification of tauopathies. In conditions of dementia, NFD (neurofibrillary degeneration) severity is correlated to cognitive impairment and is often considered as neuronal death. Using tau animal models, analysis of the kinetics of tau phosphorylation, aggregation and neuronal death in parallel to electrophysiological and behavioural parameters indicates a disconnection between cognition deficits and neuronal cell death. Tau phosphorylation and aggregation are early events followed by cognitive impairment. Neuronal death is not observed before the oldest ages. A sequence of events may be the formation of toxic phosphorylated tau species, their aggregation, the formation of neurofibrillary tangles (from pre-tangles to ghost tangles) and finally neuronal cell death. This sequence will last from 15 to 25 years and one can ask whether the aggregation of toxic phosphorylated tau species is a protection against cell death. Apoptosis takes 24 h, but NFD lasts for 24 years to finally kill the neuron or rather to protect it for more than 20 years. Altogether, these data suggest that NFD is a transient state before neuronal death and that therapeutic interventions are possible at that stage.

scholarly journals Delta-secretase-cleaved Tau antagonizes TrkB neurotrophic signalings, mediating Alzheimer’s disease pathologies

2019 ◽  
Vol 116 (18) ◽  
pp. 9094-9102 ◽  
Author(s):  
Jie Xiang ◽  
Zhi-Hao Wang ◽  
Eun Hee Ahn ◽  
Xia Liu ◽  
Shan-Ping Yu ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cell Death ◽  
Molecular Mechanisms ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Trophic Factor ◽  
Tau Pathology ◽  
Trkb Receptors ◽  
Repeat Domain

BDNF, an essential trophic factor implicated in synaptic plasticity and neuronal survival, is reduced in Alzheimer’s disease (AD). BDNF deficiency’s association with Tau pathology in AD is well documented. However, the molecular mechanisms accounting for these events remain incompletely understood. Here we show that BDNF deprivation triggers Tau proteolytic cleavage by activating δ-secretase [i.e., asparagine endopeptidase (AEP)], and the resultant Tau N368 fragment binds TrkB receptors and blocks its neurotrophic signals, inducing neuronal cell death. Knockout of BDNF or TrkB receptors provokes δ-secretase activation via reducing T322 phosphorylation by Akt and subsequent Tau N368 cleavage, inducing AD-like pathology and cognitive dysfunction, which can be restored by expression of uncleavable Tau N255A/N368A mutant. Blocking the Tau N368–TrkB complex using Tau repeat-domain 1 peptide reverses this pathology. Thus, our findings support that BDNF reduction mediates Tau pathology via activating δ-secretase in AD.

scholarly journals Activation of Divergent Neuronal Cell Death Pathways in Different Target Cell Populations during Neuroadapted Sindbis Virus Infection of Mice

2000 ◽  
Vol 74 (11) ◽  
pp. 5352-5356 ◽  
Author(s):  
Michael B. Havert ◽  
Brian Schofield ◽  
Diane E. Griffin ◽  
David N. Irani
Keyword(s):  
Cell Death ◽  
Motor Neuron ◽  
Motor Neurons ◽  
Sindbis Virus ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Lumbar Spinal Cord ◽  
Cell Death Pathways ◽  
Adult Mice ◽  
Lumbar Spinal

ABSTRACT Infection of adult mice with neuroadapted Sindbis virus (NSV) results in a severe encephalomyelitis accompanied by prominent hindlimb paralysis. We find that the onset of paralysis parallels morphologic changes in motor neuron cell bodies in the lumbar spinal cord and in motor neuron axons in ventral nerve roots, many of which are eventually lost over time. However, unlike NSV-induced neuronal cell death found in the brain of infected animals, the loss of motor neurons does not appear to be apoptotic, as judged by morphologic and biochemical criteria. This may be explained in part by the lack of detectable caspase-3 expression in these cells.

scholarly journals Lysosomal dysfunction in neurodegenerative diseases

2017 ◽  
Vol 71 (1) ◽  
pp. 0-0 ◽  
Author(s):  
Klaudia Tomala ◽  
Bożena Gabryel
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Neurodegenerative Diseases ◽  
Neurodegenerative Disorders ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Pathophysiological Mechanism ◽  
Autophagic Vacuoles ◽  
Lysosomal Dysfunction ◽  
Altered Proteins

Recent data advocate for the implication of lysosomes in the development of programmed cell death. Lysosomal dysfunction decreased the efficiency of autophagosome/lysosome fusion that leads to vacuolation of cells. Autophagic vacuoles containing damaged organelles and altered proteins are hallmarks in most neurodegenerative disorders. These aggregates consequently disrupt cellular homeostasis causing neuronal cell death due apoptosis or necrosis. Moreover calpain mediated or mutation inducted lysosomal rupture result in release of lysosomal cathepsins into the cytoplasm and inducing neuronal cell death. In this review we emphasize the pathophysiological mechanism connecting disrupting autophagy – lysosomal pathway and lysosomal dysfunction in neuronal cell death called lysosomal cell death.

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