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Received May 29, 2017; Revised Dec 15, 2017; Accepted Dec 27, 2017
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1. Introduction
Sporadic inclusion body myositis (sIBM) is a late-onset form of myopathy classified in the group of inflammatory myopathies. It is considered the most common form of myopathy in patients over 50 years of age, with a prevalence of 3,5 in 100,000 individuals and a male/female ratio of 3 : 1 [1, 2]. Whereas 18–20% of patients develop symptoms before 60 years of age, it is important to consider the diagnosis of sIBM in all patients with consistent symptoms after 30 years old [3, 4]. Clinically, the disease affects predominantly the quadriceps and the gastrocnemius muscles in the lower limbs and the finger flexors in the upper limbs [5–8]. The skeletal muscle abnormalities include an endomysial inflammatory reaction in association with degenerative changes characterized by the presence of rimmed vacuoles, intracytoplasmic inclusions formed by the accumulation of abnormal proteins, β-amyloid deposits, and mitochondrial changes [5, 9, 10]. The presence of such degenerative alterations suggests that the disease might be actually a form of muscular degeneration with an associated inflammatory reaction. This would explain the absence of a response to immunosuppressive therapy [11, 12]. However, the precise relationship between degenerative and inflammatory mechanisms is still not clear, and several lines of researches have shown that the inflammatory process could induce or even worsen the degeneration [13].
Some of the degenerative abnormalities include abnormal deposition of protein aggregates formed from amyloid precursor protein (APP), β-amyloid 42, phosphorylated tau (tau-p), α-synuclein, α-B-crystallin, clusterin, presenilin 1, gelsolin, apolipoprotein E (APOE), γ-tubulin, and numerous proteins related to oxidative stress, among them the heat shock proteins [10–15]. Interestingly, there are many similarities between the degenerative changes observed in sIBM and in Alzheimer’s and Parkinson’s diseases. These anomalies include abnormal accumulation of congophilic inclusions and many proteins with similar posttranslational modifications (i.e., α-synuclein, p62, TDP-43, LC3B, and ubiquitin), in association with inhibition of 26S proteasome and autophagic systems (defective lysosomal degradation) [11–15]. The inhibition of these two degradative systems contributes to the formation of the...