Sugarman Michael C, Kitazawa Masashi, Baker Michael, Caiozzo Vincent J, Querfurth Henry W, LaFerla Frank M
Department of Neurobiology and Behavior, University of California, 1109 Gillespie Neuroscience Facility, Irvine, CA 92697-4545, USA.
Neurobiol Aging. 2006 Mar;27(3):423-32. doi: 10.1016/j.neurobiolaging.2005.02.011. Epub 2005 Jun 13.
Inclusion body myositis (IBM) is the most common age-related degenerative skeletal muscle disorder. The aberrant intracellular accumulation of the beta-amyloid (Abeta) peptide within skeletal muscle is a pathological hallmark of IBM. Skeletal muscle is comprised of both slow and fast twitch fibers, which are present in different proportions in various muscles. It remains unclear if fast and/or slow twitch fibers are differentially involved in IBM pathogenesis. To better understand the molecular pathogenesis of IBM, we analyzed human IBM muscle biopsies and muscle from a transgenic mouse model of IBM (MCK-betaAPP). Here we report that the majority of histopathologically-affected fibers in human IBM biopsies were type II fast fibers. Skeletal muscle from MCK-betaAPP mice exhibited higher transgene expression and steady-state levels of human betaAPP in fast type IIB fibers compared to slow type I fibers. These findings indicate that fast twitch fibers may selectively accumulate and be more vulnerable to betaAPP- and Abeta-mediated damage in IBM. These findings also highlight parallels between the MCK-betaAPP mice and the human IBM condition.
包涵体肌炎（IBM）是最常见的与年龄相关的退行性骨骼肌疾病。骨骼肌中β-淀粉样蛋白（Aβ）肽的异常细胞内积聚是IBM的病理标志。骨骼肌由慢肌纤维和快肌纤维组成，它们在不同肌肉中的比例不同。目前尚不清楚快肌纤维和/或慢肌纤维是否在IBM发病机制中存在差异。为了更好地理解IBM的分子发病机制，我们分析了人类IBM肌肉活检样本以及来自IBM转基因小鼠模型（MCK-βAPP）的肌肉。在此我们报告，人类IBM活检样本中大多数组织病理学上受影响的纤维是II型快肌纤维。与慢肌I型纤维相比，MCK-βAPP小鼠的骨骼肌在快肌IIB型纤维中表现出更高的转基因表达和人βAPP的稳态水平。这些发现表明，在IBM中，快肌纤维可能选择性积聚，并且更容易受到βAPP和Aβ介导的损伤。这些发现还突出了MCK-βAPP小鼠与人类IBM病情之间的相似之处。
