Table 2.
Published studies on α-synuclein degradation
| reference | α-synuclein | UPS | ALP | model system |
|---|---|---|---|---|
| Ancolio et al. 2000 | WT & A53T | NO (Lactacystin, PSI) | n.a. | Transiently & stably transfected HEK293 cells or TSM1 neurons |
|
| ||||
| Batelli et al. 2011 | WT | NO (MG132) | Yes (3-MA) | Inducible TetOn(α-syn) PC12 cells |
| A30P | Yes (MG132) | Yes (3-MA) | ||
|
| ||||
| Bennett et al. 19910 | WT & A53T His-tagged | YES (β-lactone) | n.a. | Transiently transfected SH-SY5Y cells |
|
| ||||
| Crews et al. 2010 | WT | n.a | YES (Rapamycin, Atg7 upregulation) | Human WT α-synuclein tg mice, B103 cells |
|
| ||||
| Cuervo et al. 2004 | Rat | NO (Epoxomicin) |
YES (NH4Cl) NO (3-MA) |
Rat ventral midbrain cultures |
| WT | n.a. | YES (NH4Cl, serum removal) | Stably transfected PC12 cells & isolated lysosomes | |
| A53T, A30P | n.a. | NO (CMA) | Isolated lysosomes | |
|
| ||||
| Ebrahimi- Fakhari et al. 2011 | Mouse and human α-synuclein in α-synuclein transgenic mice; α-synuclein-eGFP in a multiphoton imaging based in vivo paradigm | YES (CLBL, MG132) | YES (BafA1, HCQ) | Human α-synuclein transgenic mice, α-synuclein-eGFP transgenic mice and non-transgenic mice |
|
| ||||
| Lee et al. 2004 | WT, A53T, A30P Myc- and His-tagged | YES for aggregates (β-lactone, epoxomicin) |
YES for aggregates (BafA1, E64, cathepsin I) NO for aggregates (3-MA, rapamycin) |
AV-mediated infection of COS-7 cells & SH-SY5Y cells Rotenone induced aggregate formation paradigm |
| n.a. | YES for oligomeric aggregates (BafA1) | |||
| NO for soluble monomer (β-lactone, epoxomicin) | NO for soluble monomer (BafA1, E64) | |||
| Rat | n.a. | YES for oligomeric aggregates (BafA1) | Rat primary cortical neurons | |
|
| ||||
| Liu et al. 2003; 2005 | WT | YES (MG132) | n.a. | Isolated 20S and 26S proteasomes |
|
| ||||
| Machiya et al. 2010 | S129P | YES (Lactacystin, MG132) | YES (3-MA, CQ) | Stably transfected SH- SY5Y cells |
| WT | NO (Lactacystin, MG132) | YES (CQ) | Stably transfected SH- SY5Y cells | |
| S129P | YES (Lactacystin, MG132) | n.a. | Rat primary cortical neurons | |
| Rat | NO (Lactacystin, MG132) | n.a. | Rat primary cortical neurons | |
|
| ||||
| Mak et al. 2010 | Mouse α-synuclein in a paraquat based overexpression model | n.a. | YES | Paraquat treated C57BL/6 mice |
|
| ||||
| Martinez- Vicente et al. 2008 | S129P; S129E; Oligomeric forms induced by nitrating agents; nitrated & dopamine modified forms WT monomers and dimers | n.a. | NO (CMA) | Isolated lysosomes |
| n.a. | YES (CMA) | |||
|
| ||||
| Paxinou et al. 2001 | WT |
YES (MG132) NO (Lactacystin) |
YES (NH4Cl) | Stably transfected HEK293 cells |
|
| ||||
| Rideout et al. 2001 | Rat | NO (Lactacystin, PSI) | n.a. | PC12 cells |
|
| ||||
| Riedel et al. 2010 | A53T | n.a. | YES (17-AAG, NH4Cl, rapamycin) | OLN-93 cells |
|
| ||||
| Rott et al. 2011 | Monoubiquitinated α-synuclein | YES (Lactacystin, MG132) | YES, but only small effect (3-MA, CQ, NH4Cl, Wortmannin) | Transfected SH-SY5Y cells |
| Deubiquitinated α-synuclein | YES, but only small effect (Lactacystin) | YES (3-MA) | ||
|
| ||||
| Sarkar et al. 2007 | WT, A53T, A30P | n.a. |
YES for A53T & A30P (Trehalose) NO for WT (Trehalose) |
Stably transfected PC12 cells |
|
| ||||
| Shin et al. 2005 | SynT (WTSynEGFPΔ 155) | YES (ALLN) | YES (NH4Cl) | Stably and transiently transfected H4 cells |
|
| ||||
| Spencer et al. 2009 | WT, Ser129P | n.a. | YES (Beclin-1 upregulation, 3-MA, BafA1, rapamycin) | B103 cells |
| WT | n.a. | YES (Beclin-1 upregulation) | Human WT α-synuclein tg mice | |
|
| ||||
| Sevlever et al. 2008 | WT | n.a. | Yes (shRNA to cathepsin D) | 3D5 cells |
|
| ||||
| Tofaris et al. 2001 | WT | YES (Lactacystin) | n.a. | Stably transfected SH-SY5Y cells & isolated 20S proteasomes |
|
| ||||
| Tofaris et al. 2011 | Ubiquitinated α-synuclein | YES, but not in Nedd4 overexpressing cells (Bortezomib) | YES (CQ, 3-MA) | SH-SY5Y and HEK293 cells |
|
| ||||
| Vogiatzi et al. 2008 | Rat & overexpressed WT | NO (Epoxomicin) | YES (3-MA, Lamp downregulation, DQWT mutant) | PC12 cells |
| WT | n.a. | YES (DQWT mutant) | SH-SY5Y cells | |
| Rat | NO (Epoxomicin) | YES (3-MA, Lamp2a downregulation) | Rat primary cortical neurons | |
| Mouse α-synuclein | n.a. | YES (Lamp2a downregulation) | Mouse primary cortical neurons | |
| Rat synuclein | n.a. | YES (Lamp2a downregulation, 3- MA) | Primary ventral mid- brain cultures | |
|
| ||||
| Webb et al. 2003 | WT, A53T, A30P HA tagged | YES (Lactacystin, epoxomicin) | YES (BafA1, 3-MA, rapamycin) | Inducible TetOn(α-syn) PC12 cells |
|
| ||||
| Wong et al. 2008 | WT α-synuclein in lactacystin induced aggresomes | n.a. | YES (Starvation, rapamycin, 3-MA) | SH-SY5Y cells |
|
| ||||
| Yamada et al. 2006 | WT, A53T, A30P Myc-His tagged | YES | n.a. | Archaeal 20S proteasomes in HEK293 & Neuro2a cells |
|
| ||||
| Yu et al. 2009 | WT, A53T | n.a | YES for oligomers (Beclin-1 downregulation, Atg5 downregulation; 3MA, rapamycin) | Transfected M17 cells |
Abbreviations: 3-MA (3-Methyladenine); AV (adenovirus); BafA1 (Bafilomycin A1); CLBL (Clasto-lactacystin β-lactone); CMA (chaperone mediated autophagy); CQ (Chloroquine); HCQ (Hydroxychloroquine); PSI (Z-lle-Glu(OtBu)-Ala-Leu-al); WT (wild type)