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] |