Table 1.
Neurological protein conformation disorders.
| Disease name |
Affected gene | Intracellular Ubiquitinated Lesion |
Major component |
Cell Type | Distribution of Inclusions |
Citations |
|---|---|---|---|---|---|---|
| HD | HD/IT-15 | DN, NII, GCI, DNS | polyQ Htt | Neurons, Glia | Ctx, hc, str, bs | (DiFiglia et al., 1997; Gutekunst et al., 1999; Maat-Schieman et al., 1999) |
| DRPLA | ATN1 | NCI, NII, DNS, GII | polyQ Atn1 | Neurons, Glia | str,bs, Ctx, dn, gp, lgn, sn, hc, cb |
(Hayashi et al., 1998a; Hayashi et al., 1998b; Yazawa, 2000) |
| SBMA | AR | NII, granules | polyQ AR | Motoneurons | bs,hyp, sn | (Adachi et al., 2005; Li et al., 1998a; Li et al., 1998b) |
| SCA1 | SCA1 | NCI, NII, DNS | polyQ Atxn1 | Neurons | Ctx, str, sn, bs, sc | (Durr et al., 1996; Duyckaerts et al., 1999; Servadio et al., 1995) |
| SCA2 | SCA2 | NCI, GCI, NII | polyQ Atxn2 | Neurons, Glia | Ctx, str, dn, gp, thal, bs, Pkj |
(Huynh et al., 1999; Huynh et al., 2000; Koyano et al., 1999; Pang et al., 2002) |
| MJD/SCA3 | SCA3 | NCI, NII, DNS | polyQ Atxn3 | Neurons | sc, dn, gp, thal, Ctx | (Durr et al., 1996; Paulson et al., 1997; Rub et al., 2006; Schmidt et al., 1998) |
| SCA6 | CACNA1A | NCI, NII | polyQ CACNA1A | Neurons | Ctx, hc, str, bd, cb, sc | (Ikeuchi et al., 1997; Ishikawa et al., 2001; Zhuchenko et al., 1997) |
| SCA7 | SCA7 | NCI, NII | polyQ Atxn7 | Neurons | lgn, bs, sn, hc, str, cb, thal, ctx |
(David et al., 1997; Einum et al., 2001; Garden et al., 2002a; Holmberg et al., 1998) |
| SCA17 | TBP | DNS, NII | polyQ TBP | Neurons | Thal, cb, bs | (Friedman et al., 2007; Nakamura et al., 2001; Rolfs et al., 2003) |
| PD DLB |
See (Moore et al., 2005) |
LB, LN** | α-synuclein | Neurons | sn>ctx, amyg amyg, ctx, hc, sn |
(Burke et al., 2008; Duda et al., 2000; Lippa et al., 2007; Markopoulou et al., 2008) |
| MSA | GCI, NCI, GII, NFT | α-synuclein, tubulin |
Glia, Neurons | Widespread; bg, cb, bs |
(Papp and Lantos, 1994; Probst-Cousin et al., 1996; Wakabayashi and Takahashi, 2006) |
|
| AD | See (Spires-Jones et al., 2009) | NFT, Threads, DN | Tau | Neurons | Ctx, hc, str, thal | (Onorato et al., 1989; Shukla and Bridges, 1999; Taraszewska et al., 1996) |
| PSP | Threads, NFTs | Tau | Neurons | str, gp, thal, cb, bs, ctx |
(Cervos-Navarro and Schumacher, 1994; Verny et al., 1996) |
|
| ALS familial | See (Wood et al., 2003) |
Hyaline inclusions | SOD1 | Neurons, Glia, Motoneurons |
sc, ctx, bs | (Mackenzie et al., 2007; Shibata et al., 1996; Wijesekera and Leigh, 2009) |
| ALS sporadic | n/a | Skeins, LB-like Bunina bodies |
TDP-43 Cystatin-C, Tf |
Neurons, Glia, Motoneurons |
bs, ctx | (Arai et al., 2006; Leigh et al., 1991; Mackenzie et al., 2007; Okamoto et al., 2008; Tan et al., 2007; Wood et al., 2003) |
| CMT2E | NEFL | NF whorls, NF islets*** | NF | Peripheral nerves |
(Fabrizi et al., 2004; Fabrizi et al., 2007; Jordanova et al., 2003) |
|
| FTLD | MAPT* | NFT, DN | Tau | Neurons, Glia | Ctx, hc, amyg, str, gp, thal, bs, cb |
(Cairns et al., 2007) |
| FTLD –U (CHMP2B) |
CHMP2B | NCI, GCI, DN, NII | Unknown (p62-& Ub-pos) |
Neurons, Glia | Ctx, hc, str, sc, bs | (Liscic et al., 2008; Schumacher et al., 2009; van der Zee et al., 2007) |
| FTLD –U types 1–3 type3 PGRN type4 |
Unknown PGRN VCP |
NCI, GCI, DN, NII | TDP-43 (p62-& Ub-pos) |
Neurons, Glia | Ctx, hc, str, sc, bs | (Davidson et al., 2007; Forman et al., 2006a; Forman et al., 2006b; Liscic et al., 2008; van der Zee et al., 2007; Watts et al., 2004) |
| FTLD with Pick bodies |
Unknown | Pick bodies | Tau, NF | Neurons, Glia | Ctx, hc, str, sc, bs | (Dickson, 2001; Uchihara et al., 2003) |
| Alexander’s disease |
GFAP | Rosenthal fibers | α-crystallin, GFAP |
Astrocytes | Widespread, ctx, ic, ec |
(Borrett and Becker, 1985; Brenner et al., 2001; Iwaki et al., 1989) |
Notes:
Other yet identified mutations may still exist (Cairns et al., 2007);
Mutations in LRRK2 may not present with LB pathology (Marti-Masso et al., 2009; Santpere and Ferrer, 2009; Zimprich et al., 2004);
not examined for ubiquitin in human samples. Ubiquitinated inclusions are observed in studies using cultured neurons(Lin and Schlaepfer, 2006).
Abbreviations: AD, Alzheimer’s disease; ALS, Amyotrophic lateral sclerosis; amyg, amygdala; ATN1, atrophin 1; ATXN, ataxin; AR, androgen receptor; bs, brain stem; CACNA1A, calcium channel, voltage-dependent, P/Q type, alpha 1A subunit ; cb, cerebellum; CMT2E, Charcot-Marie Tooth type 2E; CHMP2B, chromatin modifying protein 2B; Ctx, cortex; DLB, Dementia with Lewy Bodies; DN, Dystrophic neurites; DNS, Diffuse neuronal staining; DRPLA, dentatorubropallidoluysian atrophy; ec, external capsule; FTLD-U, frontotemporal lobar degeneration with ubiquitinated inclusions; GCI, Glial intracytoplasmic inclusions; GFAP, Glial fibrillary acid protein, GII, Glial intranuclear inclusions; gp, globus pallidus; hc, hippocampus; HD, Huntington’s disease; Htt, Huntingtin; ic, internal capsule; LB, Lewy body; lgn, lateral geniculate nucleus; LN, Lewy neurites; MAPT, microtubule-associated protein tau; MJD, Machado-Joseph’s disease; MSA, Multiple systems atrophy; NCI, Neuronal cytoplasmic inclusions; NEFL, neurofilament light chain; NF, neurofilament; NFT, Neurofibrillary tangles; NII, Neuronal intranuclear inclusions; PD, Parkinson’s disease; Pkj, Purkinje cells; PGRN, progranulin; PSP, Progressive supranuclear palsy; sc, spinal cord; SCA, spinocerebellear ataxia; sn, substantia nigra; str, striatum; TBP, TATA binding protein; TDP-43, TAR DNA binding protein-43Tf, Transferrin; thal, thalamus; Ub, ubiquitin; VCP, valosin-containing protein.