JNK-interacting protein 1 mediates Alzheimer's-like pathological features in AICD-transgenic mice
Program in Molecular Medicine
Biochemistry | Cell Biology | Cellular and Molecular Physiology | Molecular and Cellular Neuroscience | Molecular Biology
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.
AICD, APP, Alzheimer's, JNK, JNK-interacting protein 1, Tau
DOI of Published Version
Neurobiol Aging. 2015 Aug;36(8):2370-9. doi: 10.1016/j.neurobiolaging.2015.04.013. Epub 2015 Apr 30. Link to article on publisher's site
Neurobiology of aging
Margevicius, Daniel R.; Bastian, Chinthasagar; Fan, Qingyuan; Davis, Roger J.; and Pimplikar, Sanjay W., "JNK-interacting protein 1 mediates Alzheimer's-like pathological features in AICD-transgenic mice" (2015). Davis Lab Publications. 16.