Jang, Yongwoo Lee, Byeongjun Kim, Hyungsup Jung, Seungmoon Lee, Sung Hoon Lee, So-Young Jeon, Ji Hyun Kim, In-Beom Lee, Seo-Ho Kim, Byung-Ju Kim, Uh-Hyun Lee, Yunjong Kim, Sung Min Jeon, Daejong Oh, Uhtaek 2024-01-19T20:03:28Z 2024-01-19T20:03:28Z 2021-09-02 2019-05 0893-7648 https://pubs.kist.re.kr/handle/201004/120034 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. English SPRINGER Trpm2 Ablation Accelerates Protein Aggregation by Impaired ADPR and Autophagic Clearance in the Brain Article 10.1007/s12035-018-1309-0 1 MOLECULAR NEUROBIOLOGY, v.56, no.5, pp.3819 - 3832 MOLECULAR NEUROBIOLOGY 56 5 3819 3832 N scie scopus 000468535100056 2-s2.0-85053472685 Neurosciences Neurosciences & Neurology Article INCLUSION-BODIES OXIDATIVE STRESS CHANNELS RIBOSE LIPOFUSCIN CONTRIBUTES ACTIVATION REVEALS SYSTEM KINASE ADPR AMP Autophagy Protein aggregation TRPM2