| First Author | Samantha Sykioti V | Year | 2021 |
| Journal | J Neurochem | Volume | 157 |
| Issue | 6 | Pages | 2024-2038 |
| PubMed ID | 32974895 | Mgi Jnum | J:309825 |
| Mgi Id | MGI:6730212 | Doi | 10.1111/jnc.15199 |
| Citation | Samantha Sykioti V, et al. (2021) Deficiency of the serine peptidase Kallikrein 6 does not affect the levels and the pathological accumulation of a-synuclein in mouse brain. J Neurochem 157(6):2024-2038 |
| abstractText | Several lines of evidence indicate that the propagation of misfolded alpha-synuclein (alpha-syn) plays a central role in the progression and manifestation of Parkinson's disease. Pathogenic alpha-syn species can be present in the extracellular space. Thus, the identification and modulation of the key enzymes implicated in extracellular alpha-syn turnover becomes vital. Kallikrein peptidase 6 has been identified as one of the major alpha-syn degrading enzymes and has been implicated in the clearance of extracellular alpha-syn. However, the physiological role of this enzyme in regulating alpha-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 alpha-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 alpha-syn accumulation, showed that KLK6 deletion had no impact on the protein levels of intracellular or extracellular alpha-syn. Upon in vivo administration of alpha-syn pre-formed fibrils (PFF), alpha-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 alpha-syn levels observed in the A53T alpha-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 alpha-syn fibrils in alpha-syn turnover studies. |
