| Budget Amount *help |
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2017: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2016: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2015: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
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| Outline of Final Research Achievements |
Genetic variations in CDKAL1 have been associated with the development of type 2 diabetes. CDKAL1 is a methylthiotransferase that catalyzes 2-methylthi modification of tRNALys(UUU). The ms2 modification is important for accurate decoding of Lys codon in Proinsulin. In addition to Proinsulin, Lys is also critical for the processing of various neurotropic factors. We hypothesized that the dysregulation of CDKAL1 might cause aberrant translation of neurotropic factors, and lead to the development of neuropathy. To test this hypothesis, we investigated the sensory functions of peripheral nerves in Cdkal1-knockout mice. Cdkal1-deficiency induced peripheral neuropathy independent of glucose intolerance. Cdkal1-deficient mice exhibited loss of CGRP- and IB4-positive neurons in DRG. Cdkal1-deficient mice exhibited loss of nerve fibers in footpad. BDNF were reduced in DRG of Cdkal1KO mice.These results suggest that dysfunction of Cdkal1 may critical for development of diabetic neuropathy.
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