title: Pu-erh tea extract induces the degradation of FET family proteins involved in the pathogenesis of amyotrophic lateral sclerosis.
abstract: FET family proteins consist of fused in sarcoma/translocated in liposarcoma (FUS/TLS), Ewing's sarcoma (EWS), and TATA-binding protein-associated factor 15 (TAF15). Mutations in the copper/zinc superoxide dismutase (SOD1), TAR DNA-binding protein 43 (TDP-43), and FET family proteins are associated with the development of amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease. There is currently no cure for this disease and few effective treatments are available. Epidemiological studies indicate that the consumption of tea is associated with a reduced risk of developing neurodegenerative diseases. The results of this study revealed that components of a pu-erh tea extract (PTE) interacted with FET family proteins but not with TDP-43 or SOD1. PTE induced the degradation of FET family proteins but had no effects on TDP-43 or SOD1. The most frequently occurring ALS-linked FUS/TLS mutant protein, R521C FUS/TLS, was also degraded in the presence of PTE. Furthermore, ammonium chloride, a lysosome inhibitor, but not lactacystin, a proteasome inhibitor, reduced the degradation of FUS/TLS protein by PTE. PTE significantly reduced the incorporation of R521C FUS/TLS into stress granules under stress conditions. These findings suggest that PTE may have beneficial health effects, including preventing the onset of FET family protein-associated neurodegenerative diseases and delaying the progression of ALS by inhibiting the cytoplasmic aggregation of FET family proteins.
authors.affiliation: Key Laboratory for Molecular Enzymology and Engineering, The Ministry of Education, Jilin University, Changchun 130012, China ; Department of Pu-Erh Tea and Medical Science, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan ; State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China.
authors.forename: Yang
authors.identifier: 0000-0002-5444-8412
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Department of Pu-Erh Tea and Medical Science, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan ; Department of Microbiology, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan.
authors.forename: Shuhei
authors.identifier: 0000-0001-7004-7339
authors.initials: S
authors.lastname: Hayashi
authors.affiliation: Department of Pu-Erh Tea and Medical Science, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan.
authors.forename: Xianbin
authors.initials: X
authors.lastname: Cai
authors.affiliation: Department of Pu-Erh Tea and Medical Science, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan ; Key Laboratory of Pu-Erh Tea Science, The Ministry of Education, Yunnan Agricultural University, Kunming 650201, China.
authors.forename: Chongye
authors.initials: C
authors.lastname: Fang
authors.affiliation: Key Laboratory for Molecular Enzymology and Engineering, The Ministry of Education, Jilin University, Changchun 130012, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Shi
authors.affiliation: Department of Pu-Erh Tea and Medical Science, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan ; Department of Microbiology, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan.
authors.forename: Hiroko
authors.identifier: 0000-0001-7928-4875
authors.initials: H
authors.lastname: Tsutsui
authors.affiliation: Key Laboratory of Pu-Erh Tea Science, The Ministry of Education, Yunnan Agricultural University, Kunming 650201, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Sheng
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism*; D028241:Camellia sinensis / Q000737:chemistry*; D045744:Cell Line, Tumor; D057809:HEK293 Cells; D006801:Humans; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D059748:Proteolysis / Q000187:drug effects*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D013662:Tea
chemical_list: D010936:Plant Extracts; D011518:Proto-Oncogene Proteins; D013662:Tea