The heat shock response in neurons and astroglia and its role in neurodegenerative diseases

Table 4 The effect of the over-expression of Hsps and up-regulation of the HSR on the molecular pathologies developed in rodent models of HD

Transgenic model/Therapeutic compound	HD model	Increase in Hsp in Tg mouse	Extended lifespan	% ↑/↓ in surviving neurons	% ↑/↓ in levels of inclusions	References
αB-c Tg (astroglia only)	BACHD	–	–	12.5% ↑	50% ↓	[92]
Hsp27 Tg	R6/2	12-fold ↑	–	–	No ∆	[180]
Hsp70 Tg	R6/2	Rat Hsp70	–	–	No ∆	[72]
Hsp70 Tg		5–15-fold ↑ human Hsp70	No ∆	No ∆	No ∆	[181]
rAAV-QBP1-Hsc70 binding motif	R6/2	Injected into the striatum	32 days	–	90.8% ↓	[158]
rAAV-DNAJB1	R6/2	Injected into the striatum	17 days	–	39.2% ↓	[159]
DNAJB6 Tg	R6/2	Brain-specific up-regulation (nestin promoter)	21 days	–	33% ↓	[157]
HSJa Tg	R6/2	Brain specific up-regulation	No ∆	No ∆	35% ↓	[182]
Hsp104	N171-82Q HD	“Strongly” expressed in the brain, heart kidneys, testis	–	–	No ∆	[183]
HSF1^Active Tg	R6/2	Expressed in skeletal muscle, heart and testes	15 days	No ∆	79% ↓	[155]
NVP-HSP990 treatment	R6/2	2.7-fold ↑ Hsp70 3.8-fold ↑ Hsp25 1.6-fold ↑ Hsp40	No ∆	–	20% ↓	[75]
HSF1 KO	R6/2	–	105 day decrease in lifespan	–	15% ↑	[184]
HSF2 KO	R6/2	–	91 day decrease in lifespan	–	20% ↑	[185]

Double transgenic (Tg) mice were bred for the over-expression of an Hsp and polyQ-expanded Htt associated with HD. Alternatively, HSF1 and HSF2 genes were knocked-out (KO) of HD mouse models. Lentiviral vectors for the expression of QBP1-Hsc70 binding motif and DNAJB1 were injected directly into the striatum of R6/2 mice. In one case, mice that over-express polyQ-expanded Htt were treated with NVP-HSP990, a therapeutic compound for the activation of the HSR. The fold increase in Hsp levels (and, if reported, the tissue-type in which this occurs), number of extended days of life, percent increase (↑) or decrease (↓) in spinal cord motor neurons, and percent ↑ or ↓ in the levels of inclusions is reported for each study

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