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Trpm2 Ablation Accelerates Protein Aggregation by Impaired ADPR and Autophagic Clearance in the Brain

Title
Trpm2 Ablation Accelerates Protein Aggregation by Impaired ADPR and Autophagic Clearance in the Brain
Author
김성민
Keywords
ADPR; AMP; Autophagy; Protein aggregation; TRPM2
Issue Date
2019-05
Publisher
SPRINGER
Citation
MOLECULAR NEUROBIOLOGY, v. 56, NO 5, Page. 3819-3832
Abstract
TRPM2 a cation channel is also known to work as an enzyme that hydrolyzes highly reactive, neurotoxic ADP-ribose (ADPR). Although ADPR is hydrolyzed by NUT9 pyrophosphatase in major organs, the enzyme is defective in the brain. The present study questions the role of TRPM2 in the catabolism of ADPR in the brain. Genetic ablation of Trpm2 results in the disruption of ADPR catabolism that leads to the accumulation of ADPR and reduction in AMP. Trpm2(-/-) mice elicit the reduction in autophagosome formation in the hippocampus. Trpm2(-/-) mice also show aggregations of proteins in the hippocampus, aberrant structural changes and neuronal connections in synapses, and neuronal degeneration. Trpm2(-/-) mice exhibit learning and memory impairment, enhanced neuronal intrinsic excitability, and imbalanced synaptic transmission. These results respond to long-unanswered questions regarding the potential role of the enzymatic function of TRPM2 in the brain, whose dysfunction evokes protein aggregation. In addition, the present finding answers to the conflicting reports such as neuroprotective or neurodegenerative phenotypes observed in Trpm2(-/-) mice.
URI
https://link.springer.com/article/10.1007%2Fs12035-018-1309-0http://repository.hanyang.ac.kr/handle/20.500.11754/111831
ISSN
0893-7648; 1559-1182
DOI
10.1007/s12035-018-1309-0
Appears in Collections:
COLLEGE OF ART AND PHYSICAL EDUCATION[S](예술·체육대학) > PHYSICAL EDUCATION(체육학과) > Articles
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