The neuronal extracellular matrix restricts distribution and internalization of aggregated Tau-protein

Suttkus, Anne; Holzer, Max; Morawski, Markus; Arendt, Thomas

doi:10.1016/j.neuroscience.2015.11.040

Cited by 33 publications

(33 citation statements)

References 42 publications

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“…ECM components may act as a barrier restricting access to the plasma membrane: neurons with abundant ECM components are devoid of neurofibrillary tangles of tau in AD (Br€ uckner et al, 1999;H€ artig et al, 2001;Morawski et al, 2010) and are protected against Ab neurotoxicity (Miyata et al, 2007). The implication of ECM components has been reinforced by recent studies using mice lacking aggrecan (chondroitin sulfate proteoglycan), cartilage link-protein 1 (stabilizing the interaction between hyaluronic acid and proteoglycans such as aggrecan), or tenascin-R (extracellular glycoprotein) (Suttkus et al, 2016). Mouse knockout for any of the three components increased the internalization of tau protein and, consequently, increased tau spreading (Suttkus et al, 2016).…”

Section: Directed Diffusionmentioning

confidence: 99%

“…The implication of ECM components has been reinforced by recent studies using mice lacking aggrecan (chondroitin sulfate proteoglycan), cartilage link-protein 1 (stabilizing the interaction between hyaluronic acid and proteoglycans such as aggrecan), or tenascin-R (extracellular glycoprotein) (Suttkus et al, 2016). Mouse knockout for any of the three components increased the internalization of tau protein and, consequently, increased tau spreading (Suttkus et al, 2016). Other glycoproteins, such as reelin (secreted protein), were shown to protect neurons by binding soluble Ab species, thus delaying fibril formation and preventing spine loss (Pujadas et al, 2014).…”

Section: Directed Diffusionmentioning

confidence: 99%

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Physico-Pathologic Mechanisms Involved in Neurodegeneration: Misfolded Protein-Plasma Membrane Interactions

Shrivastava¹,

Aperia²,

Melki³

et al. 2017

Neuron

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Several neurodegenerative disorders, such as Alzheimer's and Parkinson's disease, are characterized by prominent loss of synapses and neurons associated with the presence of abnormally structured or misfolded protein assemblies. Cell-to-cell transfer of misfolded proteins has been proposed for the intra-cerebral propagation of these diseases. When released, misfolded proteins diffuse in the 3D extracellular space before binding to the plasma membrane of neighboring cells, where they diffuse on a 2D plane. This reduction in diffusion dimension and the cell surface molecular crowding promote deleterious interactions with native membrane proteins, favoring clustering and further aggregation of misfolded protein assemblies. These processes open up new avenues for therapeutics development targeting the initial interactions of deleterious proteins with the plasma membrane or the subsequent pathological signaling.

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Section: Directed Diffusionmentioning

confidence: 99%

Section: Directed Diffusionmentioning

confidence: 99%

Physico-Pathologic Mechanisms Involved in Neurodegeneration: Misfolded Protein-Plasma Membrane Interactions

Shrivastava¹,

Aperia²,

Melki³

et al. 2017

Neuron

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“…The chemical heterogeneity of PNs facilitated multiple detection methods including antibodies directed against different CSPGs such as aggrecan (Lander et al, 1997 ) and tenascins, but also N-acetylgalactosamine-recognizing lectins such as Wisteria floribunda agglutinin (WFA; Härtig et al, 1992 ) and Vicia villosa agglutinin (VVA; Nakagawa et al, 1986 ; Kosaka and Heizmann, 1989 ). Classical histological detection methods enabled first descriptions of nets by Camillo Golgi and Ramón y Cajal (as summarized for instance by Brauer et al, 1982 ; Bignami et al, 1992 ; Celio et al, 1998 ; Celio, 1999 ). Notably, Brauer et al ( 1982 ) introduced the term “PNs” based on Golgi impregnation techniques visualizing these web-like coatings in association with glia.…”

Section: Introductionmentioning

confidence: 99%

Damaged Neocortical Perineuronal Nets Due to Experimental Focal Cerebral Ischemia in Mice, Rats and Sheep

Härtig

Mages

Aleithe

et al. 2017

Front. Integr. Neurosci.

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As part of the extracellular matrix (ECM), perineuronal nets (PNs) are polyanionic, chondroitin sulfate proteoglycan (CSPG)-rich coatings of certain neurons, known to be affected in various neural diseases. Although these structures are considered as important parts of the neurovascular unit (NVU), their role during evolution of acute ischemic stroke and subsequent tissue damage is poorly understood and only a few preclinical studies analyzed PNs after acute ischemic stroke. By employing three models of experimental focal cerebral ischemia, this study was focused on histopathological alterations of PNs and concomitant vascular, glial and neuronal changes according to the NVU concept. We analyzed brain tissues obtained 1 day after ischemia onset from: (a) mice after filament-based permanent middle cerebral artery occlusion (pMCAO); (b) rats subjected to thromboembolic MACO; and (c) sheep at 14 days after electrosurgically induced focal cerebral ischemia. Multiple fluorescence labeling was applied to explore simultaneous alterations of NVU and ECM. Serial mouse sections labeled with the net marker Wisteria floribunda agglutinin (WFA) displayed largely decomposed and nearly erased PNs in infarcted neocortical areas that were demarcated by up-regulated immunoreactivity for vascular collagen IV (Coll IV). Subsequent semi-quantitative analyses in mice confirmed significantly decreased WFA-staining along the ischemic border zone and a relative decrease in the directly ischemia-affected neocortex. Triple fluorescence labeling throughout the three animal models revealed up-regulated Coll IV and decomposed PNs accompanied by activated astroglia and altered immunoreactivity for parvalbumin, a calcium-binding protein in fast-firing GABAergic neurons which are predominantly surrounded by neocortical PNs. Furthermore, ischemic neocortical areas in rodents simultaneously displayed less intense staining of WFA, aggrecan, the net components neurocan, versican and the cartilage link protein (CRTL) as well as markers in net-bearing neurons such as the potassium channel subunit Kv3.1b and neuronal nuclei (NeuN). In summary, theconsistent observations based on three different stroke models confirmed that PNs are highly sensitive constituents of the NVU along with impaired associated GABAergic neurons. These results suggest that PNs could be promising targets of future stroke treatment, and further studies should address their reorganization and plasticity in both stabilizing the acute stroke as well as supportive effects during the chronic phase of stroke.

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“…Protein and lipid composition of the plasma membrane and extracellular matrix components (ECM) affect the interaction with misfolded proteins, thus contributing to their binding and further aggregation. These observations were supported by experimental proofs by which, in knockout mice for any of the major component of the ECM, such as aggrecan (chondroitin sulfate proteoglycan) or tenascin-R (extracellular glycoprotein), the internalization of tau increased, as well as its spreading [81]. In addition, neurons with abundant ECM components did not show accumulation of NFTs in AD [82] and the secreted glycoprotein reelin was shown to exhibit protective neuronal activity against binding to A delaying fibril formation [83], thus leading to the postulation that ECM components may act as a barrier against misfolded assemblies at the plasma membrane.…”

Section: Interactions Between Misfolded Proteins and Plasma Membranementioning

confidence: 81%

Untangling the Prion-Like Misfolding Mechanism for Neurodegenerative Diseases

Sarnataro¹

2018

Preprint

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The misfolding and aggregation of proteins is the neuropathological hallmark of numerous diseases including Alzheimer's disease, Parkinson's disease, and prion diseases. It is believed that misfolded and abnormal -sheets forms of wild-type proteins are the vectors of these diseases by acting as seeds for the aggregation of endogenous proteins. Cellular prion protein (PrP C ) is a glycosyl-phosphatidyl-inositol (GPI) anchored glycoprotein which is able to misfold to a pathogenic isoform PrP Sc , the causative agent of prion diseases which present as sporadic, dominantly inherited and transmissible infectious disorders. Increasing evidence highlight the importance of prion-like seeding as a mechanism for pathological spread in Alzheimer's disease and tauophaty, as well as other neurodegenerative disorders.Here, we report the latest findings on the mechanisms controlling protein folding, focusing on the ER quality control of GPI-anchored proteins and describe the "prion-like" properties of amyloid- and tau assemblies. Furthermore, we highlight the importance of pathogenic assemblies interactions with protein and lipid membrane components and their implications in both prion and Alzheimer's diseases.

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The neuronal extracellular matrix restricts distribution and internalization of aggregated Tau-protein

Cited by 33 publications

References 42 publications

Physico-Pathologic Mechanisms Involved in Neurodegeneration: Misfolded Protein-Plasma Membrane Interactions

Physico-Pathologic Mechanisms Involved in Neurodegeneration: Misfolded Protein-Plasma Membrane Interactions

Damaged Neocortical Perineuronal Nets Due to Experimental Focal Cerebral Ischemia in Mice, Rats and Sheep

Untangling the Prion-Like Misfolding Mechanism for Neurodegenerative Diseases

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