@article{2997156,
    title = "Deficiency of the serine peptidase Kallikrein 6 does not affect the levels and the pathological accumulation of a-synuclein in mouse brain",
    author = "Samantha Sykioti, V. and Karampetsou, M. and Chalatsa, I. and Polissidis, A. and Michael, I.P. and Pagaki-Skaliora, M. and Nagy, A. and Emmanouilidou, E. and Sotiropoulou, G. and Vekrelli s, K.",
    journal = "Journal of Neurochemistry",
    year = "2021",
    volume = "157",
    number = "6",
    pages = "2024-2038",
    publisher = "John Wiley and Sons Inc",
    issn = "0022-3042, 1471-4159",
    doi = "10.1111/jnc.15199",
    keywords = "alcohol;  alpha synuclein;  bovine serum albumin;  carprofen;  deoxycholate sodium;  edetic acid;  genomic DNA;  glyceraldehyde 3 phosphate dehydrogenase;  horseradish peroxidase;  immunoglobulin G;  immunoglobulin Y;  kallikrein 6;  papain;  paraformaldehyde;  phosphate buffered saline;  polysorbate 20;  potassium chloride;  proteinase inhibitor;  proteinase K;  serine proteinase;  sodium chloride;  synuclein;  triton x 100;  tyrosine 3 monooxygenase;  alpha synuclein;  kallikrein;  Prss18 protein, mouse, animal cell;  animal experiment;  animal model;  animal tissue;  Article;  brain cortex;  confocal microscopy;  controlled study;  dorsal striatum;  down regulation;  enzyme linked immunosorbent assay;  exon;  fibril;  grip strength test;  immunoblotting;  immunohistochemistry;  locomotion;  mesencephalon;  microdialysis;  mouse;  mRNA expression level;  nonhuman;  novel object recognition test;  open field behavior;  Parkinson disease;  phenotype;  polyacrylamide gel electrophoresis;  polymerase chain reaction;  problem behavior;  protein degradation;  rotarod test;  working memory;  animal;  brain;  C57BL mouse;  cell culture;  female;  genetics;  knockout mouse;  male;  maze test;  metabolism;  pathology;  physiology;  synucleinopathy, alpha-Synuclein;  Animals;  Brain;  Cells, Cultured;  Female;  Kallikreins;  Male;  Maze Learning;  Mice;  Mice, Inbred C57BL;  Mice, Knockout;  Synucleinopathies",
    abstract = "Several lines of evidence indicate that the propagation of misfolded α-synuclein (α-syn) plays a central role in the progression and manifestation of Parkinson's disease. Pathogenic α-syn species can be present in the extracellular space. Thus, the identification and modulation of the key enzymes implicated in extracellular α-syn turnover becomes vital. Kallikrein peptidase 6 has been identified as one of the major α-syn degrading enzymes and has been implicated in the clearance of extracellular α-syn. However, the physiological role of this enzyme in regulating α-syn, in vivo, still remains elusive. Here, by utilizing Klk6 knock-out (Klk6−/−) mice as our experimental model, we provide insight into the physiologic relevance of endogenous KLK6 expression on α-syn processing. Behavioral phenotyping showed that Klk6−/− mice display no gross behavioral abnormalities. Further in vivo characterization of this mouse model, in the context of α-syn accumulation, showed that KLK6 deletion had no impact on the protein levels of intracellular or extracellular α-syn. Upon in vivo administration of α-syn pre-formed fibrils (PFF), α-syn pathologic accumulations were evident both in the brains of Klk6−/−mice and wt mice without significant differences. Intrastriatal delivery of active KLK6, did not affect secreted α-syn levels observed in the A53T α-syn over-expressing mice. These findings suggest that in the in vivo setting of PFF pathology induction, KLK6 alone is not able to modulate pathology transmission. Our study raises implications for the use of recombinant α-syn fibrils in α-syn turnover studies. (Figure presented.). © 2020 International Society for Neurochemistry"
}