Table 2.
Roles of Hsp70 in Neurodegenerative Disease
| Disease | Role of Hsp70 | Ref. |
|---|---|---|
| HD | Hsp70 co-localizes with polyQ aggregates | 208 |
| Hsp70 and Hsp40 prevent aggregation of purified HD exon 1 | 85 | |
| Over-expression of Hsp70 and Hsp40 reduces polyQ aggregation and cytotoxicity |
88, 208 | |
| Hsp70 inhibits polyQ-induced caspase 3 and 9 activation and M3/6 JNK phosphatase aggregation |
94, 209 | |
| Over-expression of Hsp70 does not significantly ameliorate the disease symptoms of R6/2 HD model mice |
93 | |
| HSF-1 activating compounds reduce polyQ aggregation and rescue neurodegeneration in cultured cells and HD model mice |
100, 102, 103 |
|
| SCA1 | Hsp70 over-expression suppresses neurodegeneration and improves motor function in SCA1 mice |
91 |
| SCA3 | Hsp70 co-localizes with nuclear inclusions of ataxin-3 | 89, 210 |
| Over-expression of Hsp70 suppresses polyQ-mediated neuropathy in a Drosophila model of SCA3 |
89 | |
| SCA7 | Hdj2 and Hsp70 prevent mutant ataxin-7 aggregation in cultured cells but not in a mouse model |
92 |
| SBMA | Hsp70 co-localizes with nuclear inclusions of polyQ expanded androgen receptor (AR) |
90, 211 |
| Hsp70 and Hsp40 increases the SDS-solubility and proteasomal degradation of mutated AR in cultured cells |
212 | |
| Over-expression Hsp70 ameliorates disease phenotypes in a SBMA model | 90 | |
| Oral administration of GGA, an HSF1 inducer, ameliorates the SBMA phenotype in mouse models |
101 | |
| AD-Aβ | Hsp70 and Hsp40 block in vitro Aβ self assembly | 106 |
| Hsp70 reduces steady state Aβ levels and Aβ-induced cytoxicity in cultured cells | 107 | |
| AD-Tau | Hsp70 interacts with sites in tau important for aggregation | 109 |
| Hsp70-Bag2 captures and delivers insoluble and phosphorylated tau to the proteasome for ubiquitin-independent degradation |
116 | |
| Hsp70-Bag1 associates with tau and inhibits proteasomal degradation | 115 | |
| PD | Lewy bodies contain Hsp40 and Hsp70 | 213 |
| Over-expression of Hsp70 reduces α-synuclein aggregation and cytotoxicity | 214 | |
| Hsp70 over-expression prevents dopaminergic neuronal loss in PD models | 213, 215 | |
| CF | Immature CFTR and ΔF508 CFTR form complexes with Hdj-2 and Hsc70 | 216 |
| Inactivation of Hsc70 and CHIP in cultured cell increase surface expression of ΔF508 CFTR |
217 |