Abstract
Intracellular deposits of hyperphosphorylated tau are commonly detected in tauopathies. Furthermore, these aggregates seem to play an important role in the pathobiology of these diseases. In the present study, we determined whether the recently identified neurotoxic tau45-230 fragment also formed aggregates in neurodegenerative disorders. The presence of such aggregates was examined in brain samples obtained from Alzheimer's disease (AD) subjects by means of Western blot analysis performed under non-denaturing conditions. Our results showed that a mixture of tau45-230 oligomers of different sizes was easily detectable in brain samples obtained from AD subjects. Our data also suggested that tau45-230 oligomers could be internalized by cultured hippocampal neurons, mainly through a clathrin-mediated mechanism, triggering their degeneration. In addition, in vitro aggregation studies showed that tau45-230 modulated full-length tau aggregation thereby inducing the formation of smaller, and potentially more toxic, aggregates of this microtubule-associated protein. Together, these data identified alternative mechanisms underlying the toxic effects of tau45-230.
Original language | English (US) |
---|---|
Article number | 105252 |
Journal | Neurochemistry International |
Volume | 152 |
DOIs | |
State | Published - Jan 2022 |
Funding
This work was supported by the National Institutes of Health USA grant # RO1NS090993 to AF, and grants # P30AG072977 and P30AG013854 to the Mesulan Center for Cognitive Neurology and Alzheimer's disease.
Keywords
- Alzheimer's disease
- Clathrin-mediated endocytosis
- Neuronal degeneration
- Tau aggregates
- tau internalization
ASJC Scopus subject areas
- Cellular and Molecular Neuroscience
- Cell Biology