{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nThe collection of abstracts provided does not contain any direct reference to MIR4699. Instead, they focus on the role of protein targeting to glycogen (PTG, also known as PPP1R3C), which serves as a critical scaffolding protein coordinating the activity of protein phosphatase 1 (PP1) on enzymes involved in glycogen metabolism. In several studies, overexpression of PTG was shown to markedly increase glycogen accumulation through the dephosphorylation and activation of glycogen synthase, while knockdown or genetic deletion of PTG led to dramatic reductions in glycogen levels in diverse tissues. These findings underscore PTG’s essential role in regulating cellular glucose flux and storage as glycogen in both adipocytes and liver cells."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": "\n \nThe studies also highlight the therapeutic potential of modulating glycogen synthesis in pathological conditions. In models of Lafora disease—a form of progressive myoclonus epilepsy—genetic removal or reduction of PTG alleviated the accumulation of abnormal glycogen (polyglucosan) bodies and rescued neurodegeneration and related clinical manifestations. Similarly, altering PTG expression in metabolic tissues had significant impacts on lipid accumulation, insulin sensitivity, and overall energy balance, indicating that dysregulation of the PTG-PP1 complex may underlie both neurological and metabolic disorders."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "7"}]}, {"type": "t", "text": "\n \nFinally, the regulation of PTG expression itself is shown to be under the control of key metabolic signaling pathways. Transcription factors such as FoxA2 and pathways like mTORC1/SREBP1 mediate the cAMP-dependent activation of the PTG promoter, linking PTG levels to both glycogen storage and lipid synthesis. These molecular mechanisms further explain how shifts in PTG expression influence overall energy homeostasis, exercise capacity, and glycemic control. In summary, while none of the provided abstracts offer insights into MIR4699, they collectively emphasize the pivotal function of PTG in orchestrating glycogen metabolism and its potential as a target for treating both glycogen storage diseases and metabolic dysregulation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "8", "end_ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Sean M Crosson, Ahmir Khan, John Printen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PTG gene deletion causes impaired glycogen synthesis and developmental insulin resistance."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Invest (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1172/JCI17975"}], "href": "https://doi.org/10.1172/JCI17975"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12727934"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12727934"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Cynthia C Greenberg, Kimberly N Meredith, Limei Yan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Protein targeting to glycogen overexpression results in the specific enhancement of glycogen storage in 3T3-L1 adipocytes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M303846200"}], "href": "https://doi.org/10.1074/jbc.M303846200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12805359"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12805359"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Cynthia C Greenberg, Arpad M Danos, Matthew J Brady "}, {"type": "b", "children": [{"type": "t", "text": "Central role for protein targeting to glycogen in the maintenance of cellular glycogen stores in 3T3-L1 adipocytes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.26.1.334-342.2006"}], "href": "https://doi.org/10.1128/MCB.26.1.334-342.2006"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16354703"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16354703"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Alan Cheng, Mei Zhang, Sean M Crosson, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Regulation of the mouse protein targeting to glycogen (PTG) promoter by the FoxA2 forkhead protein and by 3',5'-cyclic adenosine 5'-monophosphate in H4IIE hepatoma cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Endocrinology (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1210/en.2005-1513"}], "href": "https://doi.org/10.1210/en.2005-1513"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16627590"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16627590"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Julie Turnbull, Anna A DePaoli-Roach, Xiaochu Zhao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PTG depletion removes Lafora bodies and rescues the fatal epilepsy of Lafora disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS Genet (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pgen.1002037"}], "href": "https://doi.org/10.1371/journal.pgen.1002037"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21552327"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21552327"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Julie Turnbull, Jonathan R Epp, Danielle Goldsmith, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PTG protein depletion rescues malin-deficient Lafora disease in mouse."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Ann Neurol (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ana.24104"}], "href": "https://doi.org/10.1002/ana.24104"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24419970"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24419970"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Binbin Lu, Dave Bridges, Yemen Yang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Metabolic crosstalk: molecular links between glycogen and lipid metabolism in obesity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Diabetes (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.2337/db13-1531"}], "href": "https://doi.org/10.2337/db13-1531"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24722244"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24722244"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Xueying Ji, Shushu Wang, Hongju Tang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PPP1R3C mediates metformin-inhibited hepatic gluconeogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Metabolism (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.metabol.2019.06.002"}], "href": "https://doi.org/10.1016/j.metabol.2019.06.002"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31181215"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31181215"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Erin E Chown, Peixiang Wang, Xiaochu Zhao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "GYS1 or PPP1R3C deficiency rescues murine adult polyglucosan body disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Ann Clin Transl Neurol (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/acn3.51211"}], "href": "https://doi.org/10.1002/acn3.51211"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33034425"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33034425"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Iliana López-Soldado, Joan J Guinovart, Jordi Duran "}, {"type": "b", "children": [{"type": "t", "text": "Increased liver glycogen levels enhance exercise capacity in mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jbc.2021.100976"}], "href": "https://doi.org/10.1016/j.jbc.2021.100976"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34284060"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34284060"}]}]}]}