Table 1.
Protein components of the amyloid‐β (Aβ) and phosphorylated tau (p‐tau) intracellular inclusions and their possible functions in sporadic inclusion body myositis muscle fibers, as identified by immunohistochemical and immuno‐electron microscopical studies (see references therein). Abbreviations: NK = not known; Aβ = amyloid‐β; BACE = β‐amyloid‐converting enzyme; UBCH7 = ubiquitin conjugating enzyme H7; RNF5 = RING finger protein 5; HSP = heat‐shock protein; CHIP = carboxyl terminus of HSP70‐ interacting protein; BiP/GRP78 = immunoglobulin heavy chain‐binding protein/glucose‐regulated protein 78; ERP72 = endoplasmic reticulum protein 72 kDa; HERP = homocysteine‐induced endoplasmic reticulum protein; ERK = extracellular signal‐regulated kinase; CDK5 = cyclin‐dependent kinase 5; GSK‐3β = glycogen synthase kinase 3β; SOD = superoxide dismutase; NF‐κB = nuclear factor‐ κB; Ref1 = redox factor 1; NOS = nitric oxide synthase; SMN = survival motor‐neuron protein; PPARγ = peroxisome proliferator‐activated receptorγ; VCP = valosin containing protein; TDP‐43 = TAR DNA binding protein; LC3 = microtubule‐associated protein 1 light chain 3; RNA = ribonucleic acid.
| Aβ‐aggregates | p‐tau aggregates | References | |||
|---|---|---|---|---|---|
| Light microscopy | Electron microscopy | Light microscopy | Electron microscopy | ||
| Morphology, typical | Plaque‐like, rounded various size inclusions | 6–10 nm filaments, floccular and amorphous material | Squiggly | 15–21 nm paired‐helical filaments | 9, 10, 13, 70 |
| β‐Pleated sheet amyloid (Congo‐red+, crystal violet+) | + | + | 4, 5, 12, 69 | ||
| Proteins, various | |||||
| Aggregate‐prone proteins | |||||
| Aβ | + | + | − | − | 9, 10 |
| α‐Synuclein | + | + | − | − | 16, 85 |
| p‐Tau | − | − | + | + | 13, 70 |
| Prion protein, cellular | + | + | + | + | (11) |
| AβPP processing/Aβ deposition | |||||
| BACE1 and BACE2 | + | + | − | − | 102, 104 |
| Nicastrin | + | + | + | + | (105) |
| Presenilin1 | + | + | + | + | (15) |
| Neprilysin | + | + | NK | NK | (28) |
| NOGO B | + | + | − | − | (123) |
| Cystatin C | + | + | − | − | (103) |
| Transglutaminase 1 & 2 | + | NK | NK | NK | (30) |
| Ubiquitin–proteasome system | |||||
| Ubiquitin | + | + | + | + | (8) |
| Proteasome subunits | + | + | + | + | (45) |
| Parkin | + | + | NK | NK | (85) |
| UbcH7 | + | + | − | − | (85) |
| UBB+1 | + | + | + | + | (44) |
| RNF5 | + | NK | − | NK | (35) |
| Heat shock proteins | |||||
| Hsp70 and its cofactors | + | + | + | + | (84) |
| Hsp40 | + | + | + | + | (84) |
| CHIP | + | + | + | + | (Paciello and Askanas, unpub. obs.) |
| ER chaperones | |||||
| BiP/GRP78 | + | + | − | − | (107) |
| GRP94 | + | + | − | − | (107) |
| Calnexin | + | + | − | − | (107) |
| Calreticulin | + | + | − | − | (107) |
| ERP72 | + | + | − | − | (107) |
| HERP | + | + | − | − | (76) |
| Signal transduction components | |||||
| ERK | − | − | + | + | (115) |
| CDK5 | − | − | + | + | (116) |
| GSK‐3β | NK | NK | + | + | (117) |
| Casein kinase 1α | NK | NK | + | NK | (57) |
| Markers of oxidative stress | |||||
| Nitrotyrosine | + | + | + | + | (125) |
| SOD1 | NK | NK | NK | NK | (14) |
| Malondialdehyde | + | + | + | + | (22) |
| α1‐ Antichymotrypsin | + | NK | NK | NK | (19) |
| NFκB | NK | NK | + | + | (126) |
| Ref‐1 | + | + | + | + | (26) |
| iNOS, eNOS | − | − | + | + | (125) |
| Seleno‐glutathione peroxidase‐1 | NK | NK | NK | NK | (24) |
| Transcription components | |||||
| RNA polymeraseII | − | − | + | + | (118) |
| RNA | − | NK | + | NK | (25) |
| SMN | − | − | + | + | (23) |
| c‐Jun | + | + | + | + | (27) |
| NFκB | + | NK | + | + | (126) |
| Ref‐1 | + | + | + | + | (26) |
| PPARγ | + | + | NK | − | (77) |
| Other proteins | |||||
| Apolipoprotein E | + | + | + | + | (71) |
| Myostatin | + | + | − | − | (121) |
| VCP | NK | NK | NK | NK | (112) |
| TDP‐43 | NK | NK | NK | NK | 64, 114 |
| LC3 | + | NK | NK | NK | (67) |
| p62 | − | − | + | + | (81) |