Autophagy activation ameliorates neuronal pathogenesis of FTLD-U mice: A new light for treatment of TARDBP/TDP-43 proteinopathies

The administration of rapamycin, an MTOR-dependent autophagy activator, for the treatment of neurodegenerative diseases has been tested in several animal models. Thus, whether autophagy activation would lead to the clearance of abnormal accumulation of aggregated proteins in neurodegenerative diseas...

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Bibliographic Details
Published in:Autophagy 2013-02, Vol.9 (2), p.239-240
Main Authors: Wang, I-Fang, Tsai, Kuen-Jer, Shen, Che-Kun James
Format: Article
Language:English
Subjects:
Animals
Autophagic Punctum
Autophagy
Binding
Biology
Bioscience
Calcium
Cancer
Cell
Cycle
DNA-Binding Proteins - metabolism
Frontotemporal Dementia - etiology
Frontotemporal Dementia - therapy
FTLD-U
Landes
Mice
Mice, Transgenic
Models, Biological
neurodegeneration
Neurons - pathology
Organogenesis
Proteins
rapamycin
Signal Transduction
TDP-43
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Summary:The administration of rapamycin, an MTOR-dependent autophagy activator, for the treatment of neurodegenerative diseases has been tested in several animal models. Thus, whether autophagy activation would lead to the clearance of abnormal accumulation of aggregated proteins in neurodegenerative diseases is worthy of exploration. We have recently shown that rapamycin administration at the early pathological stage of a mouse model with frontotemporal lobar dementia (FTLD-U) characterized with cytoplasmic TARDBP/TDP-43(+)/ubiquitin(+) inclusions (UBIs) in the diseased neurons could rescue the learning/memory deficiency and the abnormal motor function disorder of the mice. This was accompanied by a decreased level of CASP3/caspase-3 and a reduction of the neuronal loss in the mouse forehead. Moreover, autophagy activation at a late pathological stage also could improve motor function, which was accompanied by a reduction of the TARDBP(+) UBIs. This study has set the principal for therapy of neurodegenerative diseases with the TARDBP protein, i.e., amyotrophic lateral sclerosis (ALS)-TDP and FTLD-TDP43, with the use of autophagy activators.
ISSN:1554-8627
1554-8635
DOI:10.4161/auto.22526