Tau mutations promote the formation of tau oligomers and filaments, which are neuropathological
signs of several tau-associated dementias. Types of neurons in the CNS are spared of
tau pathology and are surrounded by a specialized form of extracellular matrix; called perineuronal
nets (PNs). Aggrecan, the major PN proteoglycans, is suggested to mediate PNs neuroprotective
function by forming an external shield preventing the internalization of misfolded tau. We recently
demonstrated a correlation between aggrecan amount and the expression and phosphorylation of tau
in a TauP310L-acan mouse model, generated by crossbreeding heterozygous aggrecan mice with a significant
reduction of aggrecan and homozygous TauP301L mice. Neurodegenerative processes have
been associated with changes of PN structure and protein signature. In this study, we hypothesized
that the structure and protein expression of PNs in this TauP310L-acan mouse is regulated by tau.
Immunohistochemical and biochemical analyses demonstrate that protein levels of PN components
differ between TauP301LHET-acanWT and TauP301LHET-acanHET mice, accompanied by changes in
the expression of protein phosphatase 2 A. In addition, tau can modulate PN components such as
brevican. Co-immunoprecipitation experiments revealed a physical connection between PN components
and tau. These data demonstrate a complex, mutual interrelation of tau and the proteoglycans
of the PN.
| Identifer | oai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:86306 |
| Date | 29 June 2023 |
| Creators | Schmidt, Sophie, Holzer, Max, Arendt, Thomas, Sonntag, Mandy, Morawski, Markus |
| Publisher | MDPI |
| Source Sets | Hochschulschriftenserver (HSSS) der SLUB Dresden |
| Language | English |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, doc-type:article, info:eu-repo/semantics/article, doc-type:Text |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | 12040505 |
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