Table 1.

Chaperone-related therapeutic approaches in mouse models of polyQ diseases

Drug	Route/dose	Model		Therapeutic outcomes	Reference
17-AAG	Intraperitoneal (7.5 or 75 mg/kg/week)	AR-97Q (SBMA)	✓	Improved motor phenotype (rotarod, cage activity, gait pattern); alleviated aggregate formation and nuclear localization of mutant AR; reduced muscle atrophy; decreased body weight loss rate; prolonged life span	Waza et al. 2005 [49]
17-DMAG	Oral (3 or 30 mg/kg/week)	AR-97Q (SBMA)	✓	Improved motor phenotype (rotarod, cage activity, gait pattern); alleviated aggregate formation and nuclear localization of mutant AR; reduced muscle atrophy; decreased body weight loss rate; prolonged life span	Tokui et al. 2009 [50]
BAG1	Overexpression	N171-82Q (HD)	✓	Improved rotarod phenotype (only in males)	Orr et al. 2008 [43]
			×	No change in aggregate formation, body weight loss rate, life span, and clasping phenotype
GGA	Oral (~600 and 1,200 mg/kg/day)	AR-97Q (SBMA)	✓	Improved motor phenotype (rotarod, cage activity, gait pattern); alleviated aggregate formation and nuclear localization of mutant AR; reduced muscle atrophy; decreased body weight loss rate; prolonged life span	Katsuno et al. 2005 [48]
HSF1	Overexpression	R6/2 (HD)	✓	Reduced muscular atrophy and muscular inclusions; prolonged life span	Fujimoto et al. 2005 [45]
			×	No change in clasping phenotype and body weight loss rate; no reduction in brain atrophy and neuronal inclusion formation
hsp104	Overexpression	N171-82Q (HD)	✓	Reduced number of cortical aggregates; prolonged life span	Vacher et al. 2005 [42]
			×	No change in rotarod and grip strength performance; no change in body weight loss rate
Hsp70	Overexpression (5- to 10-fold of endogenous level)	AR-97Q (SBMA)	✓	Improved motor phenotype (rotarod, cage activity, gait pattern); alleviated aggregate formation and nuclear localization of mutant AR; decreased body weight loss rate; prolonged life span	Adachi et al. 2003 [47]
Hsp70	Overexpression (~10- to 20-fold of endogenous level)	B05 (SCA1)	✓	Improved rotarod phenotype; improved Purkinje cell morphology	Cummings et al. 2001 [46]
			×	No change in NII formation
Hsp70	Overexpression (5- to 15-fold of endogenous level)	R6/2 (HD)	✓	Decreased body weight loss rate	Hansson et al. 2003 [41]
			×	No change in clasping behavior; no reduction in brain atrophy and neuronal abnormal morphology; no change in NII formation and life span
Hsp70	Overexpression	R6/2 (HD)	✓	Delayed aggregate formation in hippocampal slice culture	Hay et al. 2004 [44]
			×	No change in rotarod and grip strength performance; increased body weight loss rate
HSP70/HDJ2	Overexpression (5- to 10-fold of endogenous level)	90Q R7E (SCA7)	×	No change in rod photoreceptor functions, no morphological changes of retinal layers, and no change in NII formation	Helmlinger et al. 2004 [392]
HSJ1a	Overexpression	R6/2 (HD)	✓	Reduced nuclear aggregate load; increased levels of soluble huntingtin; improved rotarod performance and forelimb grip strength; improved exploratory activity; increased BDNF level	Labbadia et al. 2012 [393]
			×	No change in body and brain weight loss rate