| Autor: |
Arne, Herring, Yvonne, Münster, Tamer, Akkaya, Sahar, Moghaddam, Katharina, Deinsberger, Jakob, Meyer, Julia, Zahel, Eduardo, Sanchez-Mendoza, Yachao, Wang, Dirk M, Hermann, Thomas, Arzberger, Sarah, Teuber-Hanselmann, Kathy, Keyvani |
| Rok vydání: |
2015 |
| Předmět: |
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| Zdroj: |
Alzheimer'sdementia : the journal of the Alzheimer's Association. 12(12) |
| ISSN: |
1552-5279 |
| Popis: |
Memory loss and increased anxiety are clinical hallmarks of Alzheimer's disease (AD). Kallikrein-8 is a protease implicated in memory acquisition and anxiety, and its mRNA is known to be up-regulated in AD-affected human hippocampus. Therefore, an involvement of Kallikrein-8 in Alzheimer's pathogenesis is conceivable but remains to be proved.We determined the cerebral expression of Kallikrein-8 mRNA and protein during the course of AD in patients and in transgenic mice and tested the impact of Kallikrein-8 inhibition on AD-related pathology in mice and in primary glial cells.Kallikrein-8 mRNA and protein were up-regulated in both species at incipient stages of AD. Kallikrein-8 inhibition impeded amyloidogenic amyloid-precursor-protein processing, facilitated amyloid β (Aβ) clearance across the blood-brain-barrier, boosted autophagy, reduced Aβ load and tau pathology, enhanced neuroplasticity, reversed molecular signatures of anxiety, and ultimately improved memory and reduced fear.Kallikrein-8 is a promising new therapeutic target against AD. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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