Abstract Details

Title Smad Ubiquitination Regulatory Factor-2 and Phosphorylated Smad2/3 Immunoreactivity in Pick's Disease

Topic Movement Disorders

Presentation(s) P04 - (-)

Poster/Presentation
Number 153

Objective

Background BACKGROUND: Smurf2 is an E3 ligase that belongs to the HECT domain ubiquitin ligase family. Smurf2 can interact with TGF-? type I receptor as well as Smad proteins, and promote their ubiquitin-dependent degradation, thereby controlling the cellular levels of these signaling mediators. We recently reported that phosphorylated tau inclusions of progressive supranuclear palsy are immunopositive not only for pSmad2/3 but also for Smurf2. The aberrant accumulation of pSmad2/3 was previously identified within phosphorylated tau inclusions in Pick's disease. These findings prompt us to speculate that Smurf2 might be involved in 3-repeat tauopathy as well as in 4-repeat tauopathy.

Design/Methods DESIGN/METHODS: Sections of frontal and temporal cortex from 14 Pick's disease and 6 control patients without neurological disease were analyzed with immunohistochemical methods usinig Smurf2, pSmad2/3, CP13 and ubiquitin antibodies.

Results RESULTS: Pick bodies and glial phosphorylated tau inclusions were immunopositive for both pSmad2/3 and Smurf2. However, Pick bodies of a single case without cortical atrophy were minimally immunoreactivity for Smurf2. The Pick cells showed patchy cytoplasmic Smurf2 and pSmad2/3 immunopositivity. Granulovacuolar degeneration was immunonegative for Smurf2. Triple immunofluorescence staining for Smurf2, pSmad2/3, and phosphorylated tau revealed co-localization of these proteins within Pick bodies and glial phophorylated tau inclusions.

Conclusions CONCLUSIONS: Our data indicates that possible disruption of TGF-? signaling pathway by the sequestration of Smurf2 and pSmad2/3 within phosphorylated tau inclusions could be an important event in the pathogenesis of Pick's disease.

Authors/Disclosures
Masataka Nakamura (Kansai Medical University) PRESENTER	Masataka Nakamura has nothing to disclose.
Melissa Murray, PhD (Mayo Clinic)	Dr. Murray has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Avid Radiopharmaceuticals. The institution of Dr. Murray has received research support from National Institute on Aging. The institution of Dr. Murray has received research support from Alzheimer's Association. The institution of Dr. Murray has received research support from Chan Zuckerberg Initiative.
	No disclosure on file
	No disclosure on file
Dennis W. Dickson, MD (Mayo Clinic)	Dr. Dickson has nothing to disclose.

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