Inhibition of neurite polarity by tau antisense oligonucleotides in primary cerebellar neurons

Cáceres, Alfredo; Kosik, Kenneth S.

doi:10.1038/343461a0

Cited by 615 publications

(392 citation statements)

References 13 publications

Supporting

Mentioning

378

Contrasting

Unclassified

Order By: Relevance

“…Tau protein is crucial for the establishment of neuronal polarity during embryonic development, for axonal transport, and for the intracellular trafficking of various molecules (Caceres & Kosik, 1990; Dawson et al , 2001; de Barreda et al , 2010; Hernandez & Avila, 2010; Llorens‐Martin et al , 2011; Sapir et al , 2012). Given the tight control of Tau expression during AHN, it is reasonable to assume that this protein plays a regulatory role in this process.…”

Section: Discussionmentioning

confidence: 99%

Novel function of Tau in regulating the effects of external stimuli on adult hippocampal neurogenesis

et al. 2016

View full text Add to dashboard Cite

Tau is a microtubule‐associated neuronal protein found mainly in axons. However, its presence in dendrites and dendritic spines is particularly relevant due to its involvement in synaptic plasticity and neurodegeneration. Here, we show that Tau plays a novel in vivo role in the morphological and synaptic maturation of newborn hippocampal granule neurons under basal conditions. Furthermore, we reveal that Tau is involved in the selective cell death of immature granule neurons caused by acute stress. Also, Tau deficiency protects newborn neurons from the stress‐induced dendritic atrophy and loss of postsynaptic densities (PSDs). Strikingly, we also demonstrate that Tau regulates the increase in newborn neuron survival triggered by environmental enrichment (EE). Moreover, newborn granule neurons from Tau−/− mice did not show any stimulatory effect of EE on dendritic development or on PSD generation. Thus, our data demonstrate that Tau−/− mice show impairments in the maturation of newborn granule neurons under basal conditions and that they are insensitive to the modulation of adult hippocampal neurogenesis exerted by both stimulatory and detrimental stimuli.

show abstract

Section: Discussionmentioning

confidence: 99%

Novel function of Tau in regulating the effects of external stimuli on adult hippocampal neurogenesis

et al. 2016

View full text Add to dashboard Cite

show abstract

“…To test whether this phenomenon reflected a retraction of previously formed axons or an impairment in axon development, the neurite outgrowth response of cultured neurons from WT and mutant animals was quantitated at different time points after plating. For this analysis, an axon-like neurite was defined as a process at least twice as long as any other neurite of the same cell, and with a minimum length of 50 m (Dotti et al, 1998;Cáceres and Kosik, 1990). The results obtained clearly revealed that neurons from MAP1B mutant mice have a selective and significant inhibition of axon formation, a phenomenon that is likely to reflect a delay in axon outgrowth and also a reduced rate of elongation (Figure 2,.…”

Section: Delayed Axonal Formation and Growth Cone Abnormalities In Cumentioning

confidence: 97%

Evidence for the Role of MAP1B in Axon Formation

González-Billault

Ávila

Cáceres

2001

MBoC

135

141

View full text Add to dashboard Cite

Cultured neurons obtained from a hypomorphous MAP1B mutant mouse line display a selective and significant inhibition of axon formation that reflects a delay in axon outgrowth and a reduced rate of elongation. This phenomenon is paralleled by decreased microtubule formation and dynamics, which is dramatic at the distal axonal segment, as well as in growth cones, where the more recently assembled microtubule polymer normally predominates. These neurons also have aberrant growth cone formation and increased actin-based protrusive activity. Taken together, this study provides direct evidence showing that by promoting microtubule dynamics and regulating cytoskeletal organization MAP1B has a crucial role in axon formation. INTRODUCTIONNeurons are highly polarized cells that contain a single long axon and multiple dendrites. Polarization occurs when one of the multiple neurites emerging from the cell body initiates a phase of rapid elongation, becoming the axon; the remaining neurites will develop as dendrites Dotti, 1997, 1999;Dotti et al., 1998). Because microtubule assembly and stabilization play an essential role in axon formation (Mitchison and Kirschner, 1989) a great deal of attention has been devoted to identify factors controlling microtubule organization and dynamics in nerve cells. Current evidence favors the view that several of the distinctive properties of neuronal microtubules, such as increased stability and spatial differentiation, arise from the developmentally regulated expression of structural microtubule-associated proteins (MAPs), which are notably abundant in neurons (Maccioni and Cambiazo, 1995). Therefore, it is likely that the expression of these proteins along neuronal development may affect neuronal polarization.MAP1B (Bloom et al., 1995) is the first MAP that is specifically expressed during neural development and that is especially prominent in neurons that are actively extending axons (Calvert and Anderton, 1985;Garner et al., 1990;Fischer and Romano-Clarke, 1991;Ulloa et al., 1993;Black et al., 1994: DiTella et al., 1996Gordon-Weeks and Fischer, 2000). These findings led to the hypothesis that MAP1B might be involved in axon formation by regulating microtubule dynamics. Evidence in favor of this proposal came from antisense experiments showing that MAP1B suppression reduces laminin-promoted axonal elongation (DiTella et al., 1996) and neurite outgrowth in PC12 cells (Brugg et al., 1993). More recently, it was shown that in Drosophila, an MAP1B-like protein is required for proper axonal and dendritic development Roos et al., 2000), and that microscale chromophore-assisted laser inactivation of phosphorylated MAP1B altered growth cone turning behavior in cultured neurons (Mack et al., 2000). The generation of MAP1B mutant mice has also provided additional important information. Despite discrepancies concerning the severity of the effects, all studies demonstrate that MAP1B-deficient mice have an impairment of brain development (Edelman et al., 1996;Takei et al., 1997; GonzalezBillault et...

show abstract

“…This is a prerequisite to establishing neuronal polarity and axonal outgrowth. 5,6 In addition, microtubules serve as tracks for the transport of cellular cargoes (vesicles, organelles) along axons and dendrites. 7 Both the dynamics and transport properties of microtubules are regulated by MAPs, such as tau.…”

Section: Cell Biology and Function Of Taumentioning

confidence: 99%

Tau-Based Treatment Strategies in Neurodegenerative Diseases

2008

View full text Add to dashboard Cite

Summary:Neurofibrillary tangles are a characteristic hallmark of Alzheimer's and other neurodegenerative diseases, such as Pick's disease (PiD), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), and frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17). These diseases are summarized as tauopathies, because neurofibrillary tangles are composed of intracellular aggregates of the microtubule-associated protein tau. The molecular mechanisms of tau-mediated neurotoxicity are not well understood; however, pathologic hyperphosphorylation and aggregation of tau play a central role in neurodegeneration and neuronal dysfunction. The present review, therefore, focuses on therapeutic approaches that aim to inhibit tau phosphorylation and aggregation or to dissolve preexisting tau aggregates. Further experimental therapy strategies include the enhancement of tau clearance by activation of proteolytic, proteasomal, or autophagosomal degradation pathways or anti-tau directed immunotherapy. Hyperphosphorylated tau does not bind microtubules, leading to microtubule instability and transport impairment. Pharmacological stabilization of microtubule networks might counteract this effect. In several tauopathies there is a shift toward four-repeat tau isoforms, and interference with the splicing machinery to decrease four-repeat splicing might be another therapeutic option.

show abstract

Inhibition of neurite polarity by tau antisense oligonucleotides in primary cerebellar neurons

Cited by 615 publications

References 13 publications

Novel function of Tau in regulating the effects of external stimuli on adult hippocampal neurogenesis

Novel function of Tau in regulating the effects of external stimuli on adult hippocampal neurogenesis

Evidence for the Role of MAP1B in Axon Formation

Tau-Based Treatment Strategies in Neurodegenerative Diseases

Contact Info

Product

Resources

About