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Selective filtering defect at the axon initial segment in Alzheimer's disease mouse models.
- Source :
-
Proceedings of the National Academy of Sciences of the United States of America . 9/30/2014, Vol. 111 Issue 39, p14271-14276. 6p. - Publication Year :
- 2014
-
Abstract
- Axon pathology has been widely reported in Alzheimer's disease (AD) patients and AD mouse models. Herein we report that increased miR-342-5p down-regulates the expression of ankyrin G (AnkG), a protein known to play a critical role in establishing selective filtering machinery at the axon initial segment (AIS). Diminished AnkG expression leads to defective AIS filtering in cultured hippocampal neurons from AD mouse models, as monitored by selective exclusion of large macromolecules from the axons. Furthermore, AnkG-deficiency impairs AIS localization of Nav 1.6 channels and confines NR2B to the somatodendritic compartments. The expression of exogenous AnkG improved the cognitive performance of 12-mo-old APP/PS1 mice; thus, our data suggest that AnkG and impairment of AIS filtering may play important roles in AD pathology. [ABSTRACT FROM AUTHOR]
- Subjects :
- *NEURONS
*AXONAL transport
*ALZHEIMER'S disease
*LABORATORY mice
*MACROMOLECULES
Subjects
Details
- Language :
- English
- ISSN :
- 00278424
- Volume :
- 111
- Issue :
- 39
- Database :
- Academic Search Index
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 98788447
- Full Text :
- https://doi.org/10.1073/pnas.1411837111