Increasingly, research suggests that neurodegenerative diseases and dementias are caused not by unique, solitary cellular mechanisms, but by multiple contributory mechanisms manifesting as heterogeneous clinical presentations. However, diverse neurodegenerative diseases also share common pathological hallmarks and cellular mechanisms. One such mechanism involves the redistribution of the microtubule associated protein tau from the axon into the somatodendritic compartment of neurons, followed by the mislocalization of tau into dendritic spines, resulting in postsynaptic functional deficits. Here we review various signaling pathways that trigger the redistribution of tau to the cell body and dendritic tree, and its mislocalization to dendritic spines. The convergence of multiple pathways in different disease models onto this final common pathway suggests that it may be an attractive pathway to target for developing new treatments for neurodegenerative diseases.
Bibliographical noteFunding Information:
The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: NIH Grant Numbers R61 NS115089-01 (DL); R21-NS084007-01 (DL); R21-NS096437-01 (DL); R01-NS79374 (KHA); R01-AG60766 (KHA); Michael J. Fox Foundation Grant (DL); UMN-Mayo Partnership Grant (DL); Minnesota Higher Education Grant (DL).
© The Author(s) 2020.
- AMPA receptors
- Alzheimer’s disease
- Huntington’s disease
- Parkinson’s disease
- dendritic spines
- neuronal polarity
- synaptic plasticity
PubMed: MeSH publication types
- Journal Article
- Research Support, N.I.H., Extramural
- Research Support, Non-U.S. Gov't