Skip to main content

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