Inclusion body myositis, sporadic accumulation

Oxidative damage to cells is a common phenomenon, and quality control of modified proteins is important to maintain normal cellular functions. In the cytoplasm, nucleus, and endoplasmic reticulum, the proteasome is involved in the removal of various types of proteins such as ubiquinated, misfolded, or unfolded proteins, and oxidized proteins. Abnormal inhibition of proteasome may contribute to neuro-degenerative diseases such as Alzheimer disease, Parkinson disease, Lewy body dementia, and Huntington disease [31-40]. Neuromuscular diseases, such as sporadic inclusion-body myositis (s-IBM) share several phenotypes described in the brain tissues of Alzheimer and Parkinson disease patients [41]. One such similarity to Alzheimer disease is the accumulation of amyloid-P (AP), phosphory-lated tau (p-tau), and ubiquitin, which are often found within these aggregates [42, 43]. In s-IBM patients, significant proteasome abnormalities were identified including, increased 26 S proteasome expression and abnormal accumulation of 26S proteasome, but reduced proteasome activities [44]. The inverse relationship between increased expression... 

Pathogenesis of sporadic inclusion-body myositis role of aging and muscle-fiber degeneration, and accumulation of the same proteins as in Alzheimer and Parkinson brains... 

Vattemi G, Nogalska A, King Engel W et al. (2009) Amyloid-beta42 is preferentially accumulated in muscle fibers of patients with sporadic inclusion-body myositis. Acta Neuropathol 117, 569-574. 

Nogalska A, Terracciano C, D Agostino C et al. (2009) p62/SQSTMl is overexpressed and prominently accumulated in inclusions of sporadic inclusion-body myositis musde fibers, and can help differentiating it from polymyositis and dermatomyositis. Acta Neuropathol 118, 407-413. 

Broccolini A Mirault MB, Engel WK et al. (1999) Abnormal accumulation of seleno-glutathion peroxidase-1 and catalase and their mRNAs in sporadic inclusion-body myositis. Neurology 52 (Suppl. 2), A333. 

Muth IE, Barthel K, Bahr M et al. (2009) Proinflam -matory cell stress in sporadic inclusion body myositis muscle overexpression of aB-crystallin is associated with amyloid precursor protein and accumulation of p-amyloid. J Neurol Neurosurg Psychiatry 80, 1344-1349. 

Specifically, the similarities of sporadic inclusion-body myositis with the Alzheimer brain include accumulations of amyloid-P, phosphorylated tau and numerous other "Alzheimer disease-characteristic" proteins. The similarities of inclusion-body myositis with Parkinson disease include accumulations of a-synuclein, parkin, DJ-1, and other abnormalities. These similarities suggest that (a) the aging-associated degenerative-muscle and degenerative-brain diseases may share certain pathogenic steps and (b) knowledge of one disease might help elucidate the cause and treatment of the others. And, despite the remarkable molecular sim-... 

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