Premium
P2‐069: NEUROPROTECTIVE AND BLOOD‐BRAIN‐BARRIER PENETRABLE CARBAZOLE‐BASED COMPOUNDS FOR AD TREATMENT
Author(s) -
Li HungWing,
Poon ChungYan,
Ng Olivia T.W.,
Yung KinLam,
Wong Man Shing
Publication year - 2014
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2014.05.743
Subject(s) - neuroprotection , cytotoxicity , blood–brain barrier , pharmacology , chemistry , amyloid (mycology) , in vivo , neurotoxicity , genetically modified mouse , medicine , transgene , in vitro , biochemistry , pathology , toxicity , central nervous system , biology , organic chemistry , microbiology and biotechnology , gene
on APP and A b expressions. YU101, a selective inhibitor of chymotrypsinlike activity of the 20S proteasome, significantly inhibited APP degradation and increased A b generation.Conclusions: In a Drosophila study, the overexpressed Tpr2 suppressed polyglutamine-induced ocular neurodegeneration. Co-chaperone Tpr2 contains two chaperone-binding TPR domains, each of which has seven tetratricopeptide repeat motifs, and a C-terminal DNA J homologous J domain. Tpr2 was highly expressed in astrocytes as well as in neurons in the AD mouse brain. Our results suggest that the ubiquitin-proteasome system is involved in the regulatory mechanism in APP amyloidogenesis and that the anti-amyloidogenic effect of Tpr2 includes important mechanisms of selective proteasome activation and neurodegeneration inhibition. Therefore, the proteasome-dependent trafficking pathway of APP associated with Tpr2 may be a valid therapeutic target for altering A b production in AD brain.