Premium
P1–120: Correlation between autophagy and cognitive impairment in people with Alzheimer's disease
Author(s) -
Jia Jianping,
Tang Yi,
Xing Yi
Publication year - 2013
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.2013.05.342
Subject(s) - autophagy , dementia , clinical dementia rating , cognition , disease , medicine , alzheimer's disease , psychology , biology , psychiatry , apoptosis , biochemistry
Background: The Smad ubiquitination regulatory factor 1 (Smurf1) is one of the E3 ubiquitin ligases and is related to multiple biological processes. Despite the various roles played by this protein, there is no report on the function of Smurf1 in neurodegeneration. In this study, we used immunohistochemistry to examine whether Smurf1 plays a role in the neurodegeneration observed in the brains of patients with Alzheimer’s disease (AD). Methods:We examined the brains of patients with AD immunohistochemically by using various antibodies against Smurf1. To elucidate the characteristics of Smurf1-positive structures, we examined the co-localization of Smurf1 with other proteins (actin and the Amyloid Precursor Protein (APP) C terminal) using confocal microscopy. We also tried to address the precise Smurf1 localization in a cell culture system via treatment with the actin-depolymerising toxin jasplakinolide (jpk). Results: Anti-Smurf1 antibodies immunolabelled rod-shaped, ovoid or spherical structures with morphological features that were similar to those of Hirano bodies (HBs). Double immunohistochemistry demonstrated that Smurf1 co-localized with component proteins of HBs. An immunocytochemical study revealed that Smurf1 localized in the HB model structures formed by jpk in cultured cells. Moreover, HBs were not immunolabelled by anti-autophagosomal marker antibodies, but were immunolabelled by anti-lysosomal marker antibodies. Conclusions: Smurf1 localized in HBs in AD brains and in HB model structures in cultured cells. One explanation for the immunolabelling of HBs by anti-Smurf1 antibodies is the function of Smurf1 in actin arrangements; another possibility is the function of Smurf1 in the autophagy-lysosome system. Table 1 Profiles of the subjects and frequency of immunopositive HBs