| First Author | Margevicius DR | Year | 2015 |
| Journal | Neurobiol Aging | Volume | 36 |
| Issue | 8 | Pages | 2370-9 |
| PubMed ID | 26022769 | Mgi Jnum | J:224473 |
| Mgi Id | MGI:5662331 | Doi | 10.1016/j.neurobiolaging.2015.04.013 |
| Citation | Margevicius DR, et al. (2015) JNK-interacting protein 1 mediates Alzheimer's-like pathological features in AICD-transgenic mice. Neurobiol Aging 36(8):2370-9 |
| abstractText | Amyloid precursor protein, which generates amyloid beta peptides, is intimately associated with Alzheimer's disease (AD) pathogenesis. We previously showed that transgenic mice overexpressing amyloid precursor protein intracellular domain (AICD), a peptide generated simultaneously with amyloid beta, develop AD-like pathologies, including hyperphosphorylated tau, loss of synapses, and memory impairments. AICD is known to bind c-Jun N-terminal kinase (JNK)-interacting protein 1 (JIP1), a scaffold protein that associates with and activates JNK. The aim of this study was to examine the role of JIP1 in AICD-induced AD-like pathologies in vivo, since the JNK pathway is aberrantly activated in AD brains and contributes to AD pathologies. We generated AICD-Tg mice lacking the JIP1 gene (AICD; JIP1(-/-)) and found that although AICD; JIP1(-/-) mice exhibit increased AICD, the absence of JIP1 results in decreased levels of hyperphosphorylated tau and activated JNK. AICD; JIP1(-/-) mice are also protected from synaptic loss and show improved performance in behavioral tests. These results suggest that JIP1 mediates AD-like pathologies in AICD-Tg mice and that JNK signaling may contribute to amyloid-independent mechanisms of AD pathogenesis. |
