Abstract：
:Neuroinflammation is the important pathological feature of Alzheimer's disease (AD). Legumain, a lysosomal cysteine protease, plays an important role in neuroinflammation during ischemic stroke and depressive disorder. Legumain is involved in AD process through cleaving APP; however, it is unclear if legumain can possibly modulate neuroinflammation without cleaving APP in AD. Thus, we established a mouse model of AD by single intracerebroventricular injections of Aβ1-42 in legumain knockout (KO) mice. The behavioral tests showed that legumain-KO effectively ameliorated cognitive impairment induced by Aβ1-42. Moreover, legumain deprivation significantly improves the synaptic plasticity damages in Aβ1-42-treated mice. Moreover, legumain-KO considerably inhibited the activation of microglia and reduced the expression of inflammatory cytokines in the hippocampus of Aβ1-42-treated mice. Interestingly, we found that legumain-KO inhibited TLR4/MyD88/NF-κB pathway, which was activated by Aβ1-42 in the hippocampus. In conclusion, our results suggested that legumain-KO reduced the level of neuroinflammation that was associated with inhibiting TLR4/MyD88/NF-κB pathways, thereby improving the hippocampal synaptic plasticity and reducing the cognitive impairments in Aβ1-42-treated mice. Legumain knockout blocked microglia activation by inhibiting TLR4/MyD88/NF-κB signaling pathways, and further reduced inflammatory cytokine expression. As a result, legumain knockout alleviated synaptic damage and cognitive impairment induced by Aβ1--42.
journal_name
Mol Neurobioljournal_title
Molecular neurobiologyauthors
Chen R,Zhang Q,Yan Y,Zhang Y,Zhang Tdoi
10.1007/s12035-020-02219-3subject
Has Abstractpub_date
2020-11-21 00:00:00eissn
0893-7648issn
1559-1182pii
10.1007/s12035-020-02219-3pub_type
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