{
    "abstract": "Metabolic and neurological disorders commonly display dysfunctional branched-chain amino acid (BCAA) metabolism, though it is poorly understood how this leads to neurological damage. We investigated this by generating Drosophila mutants lacking BCAA-catabolic activity, resulting in elevated BCAA levels and neurological dysfunction, mimicking disease-relevant symptoms. Our findings reveal a reduction in neuronal AMP-activated protein kinase (AMPK) activity, which disrupts autophagy in mutant brain tissues, linking BCAA imbalance to brain dysfunction. Mechanistically, we show that excess BCAA-induced mitochondrial reactive oxygen species (ROS) triggered the binding of protein phosphatase 2\u2009A catalytic subunit (PP2Ac) to AMPK, suppressing AMPK activity. This initiated a dysregulated feedback loop of AMPK-mitochondrial interactions, exacerbating mitochondrial dysfunction and oxidative neuronal damage. Our study identifies BCAA imbalance as a critical driver of neuronal damage through AMPK suppression and autophagy dysfunction, offering insights into metabolic-neuronal interactions in neurological diseases and potential therapeutic targets for BCAA-related neurological conditions.",
    "authors": [
        {
            "affiliation": "Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, 10048, Taiwan. shihchengwu@ntu.edu.tw.\nDepartment of Laboratory Medicine, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, 10021, Taiwan. shihchengwu@ntu.edu.tw.",
            "firstname": "Shih-Cheng",
            "initials": "SC",
            "lastname": "Wu"
        },
        {
            "affiliation": "National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan, 350401, Taiwan.\nInstitute of Molecular and Cellular Biology, National Taiwan University, Taipei, 10617, Taiwan.",
            "firstname": "Yan-Jhen",
            "initials": "YJ",
            "lastname": "Chen"
        },
        {
            "affiliation": "Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, 10048, Taiwan.",
            "firstname": "Shih-Han",
            "initials": "SH",
            "lastname": "Su"
        },
        {
            "affiliation": "National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan, 350401, Taiwan.",
            "firstname": "Pai-Hsiang",
            "initials": "PH",
            "lastname": "Fang"
        },
        {
            "affiliation": "National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan, 350401, Taiwan.\nInstitute of Bioinformatics and Systems Biology, National Yang Ming Chiao Tung University, Hsinchu, 300093, Taiwan.",
            "firstname": "Rei-Wen",
            "initials": "RW",
            "lastname": "Liu"
        },
        {
            "affiliation": "National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan, 350401, Taiwan.",
            "firstname": "Hui-Ying",
            "initials": "HY",
            "lastname": "Tsai"
        },
        {
            "affiliation": "Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, 10048, Taiwan.",
            "firstname": "Yen-Jui",
            "initials": "YJ",
            "lastname": "Chang"
        },
        {
            "affiliation": "National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan, 350401, Taiwan.\nDivision of Biological Sciences, Section of Cell and Developmental Biology, University of California, San Diego, La Jolla, CA, 92093, USA.",
            "firstname": "Hsing-Han",
            "initials": "HH",
            "lastname": "Li"
        },
        {
            "affiliation": "National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan, 350401, Taiwan.",
            "firstname": "Jian-Chiuan",
            "initials": "JC",
            "lastname": "Li"
        },
        {
            "affiliation": "National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan, 350401, Taiwan. chunhong@gmail.com.\nNational Mosquito-Borne Diseases Control Research Center, National Health Research Institutes, Zhunan, 350401, Taiwan. chunhong@gmail.com.",
            "firstname": "Chun-Hong",
            "initials": "CH",
            "lastname": "Chen"
        }
    ],
    "conclusions": null,
    "copyrights": "\u00a9 2025. The Author(s).",
    "doi": "10.1038/s42003-025-07457-6",
    "journal": "Communications biology",
    "keywords": [],
    "methods": null,
    "publication_date": "2025-01-22",
    "pubmed_id": "39838082\n29570613\n33050626\n35409380\n21484869\n28919799\n33024014\n29802157\n31177572\n31980395\n12522\n23478409\n14184314\n16365091\n16579849\n22730471\n32680850\n21803516\n22257881\n18191218\n19264097\n30018090\n18006683\n19725772\n8223268\n22424226\n18347073\n25199830\n24726383\n28622524\n28974774\n29895585\n19653858\n29153408\n27491897\n23211361\n22619229\n24506865\n20729205\n17602868\n30979885\n24987008\n34061429\n30376218\n32290794\n12456885\n25598486\n14965354\n17255104\n32277029\n29221169\n16957085\n34241636\n1325671\n10978272\n18299321\n33053153\n35879463\n34472622\n26683372\n21768291\n22660331\n33298971\n24928662\n24220995\n37910283\n19604711\n22367557\n30411223\n22443683\n35820485\n21755039\n33617923\n35124206\n23077661\n18194654\n24002648\n17360644\n21719444\n20516177\n18574253\n31822473\n34330816\n28634323\n26451484",
    "results": null,
    "title": "Dysfunctional BCAA degradation triggers neuronal damage through disrupted AMPK-mitochondrial axis due to enhanced PP2Ac interaction.",
    "xml": "<Element 'PubmedArticle' at 0x788503711760>"
}