[Abstract Title]. - Society for Neuroscience

Poster
244. Abeta Toxicity I
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 244.21/N2
Topic: C.01.c. Abeta toxicity
Support: NIH Grant NS41373
Title: Foxo/Atrogin induction in skeletal muscle by intracellular β-amyloid
Authors: *H.-K. LEE 1 , E. ROCNIK 1 , K. WALSH 2 , Q. FU 1 , K. M. ROSEN 1 , H. W.
QUERFURTH 1 ;
1 Neurol., Caritas St. Elizabeth's Med. Ctr., Boston, MA; 2 Cardiovasc. Resarch, Boston Univ.
Sch. of Med., Boston, MA
Abstract: Skeletal muscle atrophy is an outcome of: fasting, disuse, drug use (steroids),
spaceflight, altitude, systemic cancer or inflammatory disorders, neurogenic as well as local
dystrophic or myositic processes. In atrophic muscles, the ubiquitin ligase atrogin-1 (MAFbx) is
induced. Accumulations of intracellular β-amyloid (Aβi), tau, and inflammatory markers are
found pathologically in Inclusion Body Myositis (IBM) in which selective muscle groups
undergo atrophy. Toxicity of Aβi has been shown in cultures of skeletal muscle and neuronal
cells as well as in transgenic mice. We found that human IBM samples show increased
expression of atrogin-1 mRNA. In differentiated C2C12 myotubes, intracellular Aβ expression
caused increased expression of Atrogin mRNA and a reduction in myotube diameter, which
could be partially reversed with myristoylated Akt and dnFoxo3A. Foxo3A was localized in the
nucleus of select IBM myofibers as compared to age-matched controls. Similar results were seen
in C2C12 myotubes expressing intracellular Aβ. In conclusion, Aβi is related to Akt
deactivation, downstream activation of Foxo/Atrogin-1 and skeletal muscle atrophy.
Disclosures: H. Lee , None; E. Rocnik, None; K. Walsh, None; Q. Fu, None; K.M. Rosen,
None; H.W. Querfurth, None.
Poster
244. Abeta Toxicity I