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Table 3 The effect of the over-expression of Hsps and up-regulation of the HSR on the molecular pathologies developed in rodent models of MND

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

Transgenic model/Therapeutic compound MND model Increase in Hsp in Tg mouse Extended lifespan % ↑/↓ in surviving motor neurons % ↑/↓ in levels of inclusions References
Hsp27 Tg SOD1G93A 40-fold ↑spinal cord
25-fold ↑ cortex, cerebellum, hippocampus
Expressed in MN + GFAP+ve astroglia
No ∆ (prolonged 4.2 days) No ∆ [146]
SOD1G93A No ∆ (died 6 days sooner) 24% ↑ No ∆ [147]
HSJ1a Tg SOD1G93A 7-fold ↑ No ∆ 61% ↑ No ∆ [148]
Hsp70 Tg SOD1G93A 10-fold ↑ No ∆ (prolonged 1.4 days) [145]
SOD1G85R 10-fold ↑ spinal cord No ∆
SOD1G37R 10-fold ↑ No ∆
Hsp70 administered exogenously SOD1G93A rhHsp70 injected 3× weekly (20μg)- detected in muscle not CNS 9 days 12.5% ↑ [149]
HSF1 Tg SOD1H46R/H48Q 3-fold ↑ No ∆ 34% ↓ [151]
SIRT1 Tg SOD1G93A 3-fold ↑ 15 days 40% ↓ [150]
Withaferin A SOD1G93A 2.6-fold ↑ Hsp25
2.2-fold ↑ Hsp70
Phosphorylated HSF1
8 days 30% ↑ 39% ↓ [152]
SOD1G37R 18 days
Celastrol SOD1G93A 16 days 30% ↑ [153]
Arimoclomol SOD1G93A 3-fold ↑ Hsp70
2.5-fold ↑ Hsp90
Phosphorylated HSF1
28 days 74% ↑ [154]
NXD30001 SOD1G93A No ↑ in Hsps in the CNS
↑ Hsp70 in skeletal muscle
[170]
  1. Double transgenic (Tg) mice were bred for the over-expression of an Hsp and a SOD1 mutant associated with ALS. Alternatively, mice that over-express mSOD1 were treated with 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