Table 2.

Overview of measurements of the functionality of the ubiquitin/proteasome system in neurodegenerative disease models.

Disease	Protein context	Model system	Readout	Reduced function?	References
Polyglutamine disease	Htt fragment	Yeast	Ub-R/P-lacZ; CPY*-HA	Yes	Duennwald and Lindquist, 2008
		HEK293 cell line	GFPu	Yes	Bence et al., 2001
			NES/NLS-GFPu	Yes	Bennett et al., 2005
			UbG76V-GFP; Ub-R-GFP; GFP-CL1; ODC-GFP; GFP-dF508CFTR; TCRalpha-GFP	Yes	Hipp et al., 2012
		PC12 cell line	Ub-R/P-GFP; CD3delta-HA	Yes	Duennwald and Lindquist, 2008
			UbG76V-YFP; YFP-CL1	Yes	Maynard et al., 2009
		R6/2 mice	GFPu	No	Bett et al., 2009
			UbG76V-GFP	No	Maynard et al., 2009
		HD94 mice	UbG76V-GFP	Yesa	Ortega et al., 2010
	Ataxin-1	HEK293T cell line	d2EGFP (ODC)	Yes	Park et al., 2005
		HEK293 cell line	NES/NLS-GFPu	Yes	Bennett et al., 2005
	Ataxin-7	Sca7266Q/5Q mice	UbG76V-GFP	No	Bowman et al., 2005
	Androgen receptor	HEK293 cell line	GFPu	Yesb	Mandrusiak et al., 2003
		NSC34 cell line	YFPu, NES/NLS-YFPu	Yesc	Rusmini et al., 2007
		AR121Q flies	GFPu	Yesb	Pandey et al., 2007
		AR97Q mice	UbG76V-GFP	No	Tokui et al., 2009
Alzheimer's disease	β-amyloid peptide	B103 cell line	GFPu	Yes	Song et al., 2003; Oh et al., 2005
		HEK293 cell line	ZsProsensor (ODC)	Yes	Tseng et al., 2008
	Ubiquilin-1	HEK293T cell line	UbG76V-YFP	No	Viswanathan et al., 2011
	APPswePS1dE9 mice		UbG76V-GFP	No	Orre et al., 2013
			GFPu	Yes	Liu et al., 2014a
Parkinson's disease	α-synuclein	Yeast	GFPu	Yes	Outeiro and Lindquist, 2003
	LRRK2	HeLa cell line	UbG76V-GFP	Yes	Lichtenberg et al., 2011
ALS	SOD1	NSC34 cell line	YFPu	Yes	Crippa et al., 2010; Onesto et al., 2011
			NES/NLS-YFPu	No	Sau et al., 2007
		C2C12 cell line	YFPu	No	Onesto et al., 2011
		SOD1G93A mice	UbG76V-GFP	Yesd	Cheroni et al., 2009
ALS/IBMPFD	VCP	U2OS cell line	dF508CFTR	Yes	Weihl et al., 2006
		Meljuso cell line	UbG76V-GFP; CD3delta-GFP	No	Tresse et al., 2010
Retinal degeneration	Rhodopsin mutant	HEK293 cell line	GFPu	Yes	Illing et al., 2002
			NES/NLS-GFPu	Yes	Bennett et al., 2005
		P23H, Rho-/-, and Rds mice	UbG76V-GFP	Yes	Lobanova et al., 2013
	Transducin γ-subunit	G-/-γ1mice	UbG76V-GFP	Yes	Lobanova et al., 2013
Prion disease	Prion protein	N2aPK-1 cell line	UbG76V-GFP	Yes	Kristiansen et al., 2007
		Prion-infected mice	UbG76V-GFP	Yes	Kristiansen et al., 2007

^aTransient UPS impairment.

^bUPS impairment by mutant AR is ligand-dependent.

^cUPS impairment by mutant AR occurs only in absence of ligand; ligand treatment restored UPS functionality.

^dReduced UPS activity observed only at late stages in cells which display advanced ALS pathology (e.g., enlarged vacuoles).