| First Author | Suttkus A | Year | 2016 |
| Journal | Neuroscience | Volume | 313 |
| Pages | 225-35 | PubMed ID | 26621125 |
| Mgi Jnum | J:231382 | Mgi Id | MGI:5770505 |
| Doi | 10.1016/j.neuroscience.2015.11.040 | Citation | Suttkus A, et al. (2016) The neuronal extracellular matrix restricts distribution and internalization of aggregated Tau-protein. Neuroscience 313:225-35 |
| abstractText | Alzheimer's disease (AD) is a chronic degenerative disorder characterized by fibrillary aggregates of Ass and Tau-protein. Formation and progression of these pathological hallmarks throughout the brain follow a specific spatio-temporal pattern which provides the basis for neuropathological staging. Previously, we could demonstrate that cortical and subcortical neurons are less frequently affected by neurofibrillary degeneration if they are enwrapped by a specialized form of the hyaluronan-based extracellular matrix (ECM), the so called 'perineuronal net' (PN). PNs are composed of large aggregating chondroitin sulfate proteoglycans connected to a hyaluronan backbone, stabilized by link proteins and cross-linked via tenascin-R. Recently, PN-associated neurons were shown to be better protected against iron-induced neurodegeneration compared to neurons without PN, indicating a neuroprotective function. Here, we investigated the role of PNs in distribution and internalization of exogenous Tau-protein by using organotypic slice cultures of wildtype mice as well as mice lacking the ECM-components aggrecan, HAPLN1 or tenascin-R. We could demonstrate that PNs restrict both distribution and internalization of Tau. Accordingly, PN-ensheathed neurons were less frequently affected by Tau-internalization, than neurons without PN. Finally, the PNs as well as their three investigated components were shown to modulate the processes of distribution as well as internalization of Tau. |
