Aberrant expression of cyclin-dependent kinase 5 in inclusion body myositis

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Abstract
Objective: To investigate abnormal protein expression in inclusion body myositis (IBM). Background: In IBM, ectopic deposition of β-amyloid protein as well as several other proteins in some muscle fibers occurs. Some, but not all, of these proteins are also expressed in myofibrillar myopathy (MFM). The authors recently reported aberrant expressions of several cyclin-dependent kinases (CDKs)—enzymes regulating the cell replication cycle—in MFM. They therefore tested the notion that aberrant expression of CDKs also occurs in IBM. Among CDKs, CDK1, CDK2, and CDK5 have been demonstrated to phosphorylate tau, which is a component of inclusions in IBM. CDK5 appears in a stage of myogenesis when CDK1 and CDK2 are downregulated. Methods: Cryostat sections of muscle specimens from 10 patients with sporadic IBM were immunostained for CDK1, CDK2, and CDK5. Fourteen patients with polymyositis and eight individuals with dermatomyositis served as disease control subjects. Results: In IBM, numerous CDK5-positive inclusions were present in vacuolated fibers. CDK5 expression was not observed in any disease control subject. Regenerating fibers expressed CDK1 and CDK2 in all diseases. Conclusion: The results suggest that cyclin-dependent kinases (CDK)5, but no other CDKs, is involved in the formation of inclusions in IBM.