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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

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

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]
  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]
HSF1Active 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]
  1. 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