HSP70 (Heat Shock Protein 70)
<div class="infobox infobox-gene">
<table>
<tr><th colspan="2" style="background:#e8f4ea;">HSP70 (Heat Shock Protein 70)</th></tr>
<tr><td><b>Gene Symbol</b></td><td>HSP70 / HSPA1A / HSPA1B</td></tr>
<tr><td><b>Full Name</b></td><td>Heat Shock Protein Family A (Hsp70) Member 1A/1B</td></tr>
<tr><td><b>Chromosomal Location</b></td><td>6p21.33 (HSPA1A), 6p21.33 (HSPA1B)</td></tr>
<tr><td><b>NCBI Gene ID</b></td><td>[3309](https://www.ncbi.nlm.nih.gov/gene/3309) (HSPA1A), [3312](https://www.ncbi.nlm.nih.gov/gene/3312) (HSPA1B)</td></tr>
<tr><td><b>UniProt ID</b></td><td>[P0DMV8](https://www.uniprot.org/uniprot/P0DMV8)</td></tr>
<tr><td><b>OMIM</b></td><td>140100</td></tr>
<tr><td><b>Associated Diseases</b></td><td>[Alzheimer's Disease](/diseases/alzheimers-disease), [Parkinson's Disease](/diseases/parkinsons-disease), [ALS](/diseases/amyotrophic-lateral-sclerosis), Huntington's Disease</td></tr>
</table>
</div>
Pathway Diagram
Mermaid diagram (expand to render)
Overview
HSP70 is a human gene whose product the HSP70 family of proteins constitutes a highly conserved group of molecular chaperones that play critical roles in protein homeostasis, folding, and quality control within cells[@mayer2005]. These proteins utilize ATP-dependent mechanisms to facilitate the refolding of misfolded proteins, prevent protein aggregation, and assist in the translocation of polypeptides across cellular membranes[@rosenzweig2019]. Variants in HSP70 have been implicated in Alzheimer's Disease, Parkinson's Disease, Amyotrophic Lateral Sclerosis (ALS). This page covers the gene's normal function, disease associations, expression patterns, and key research findings relevant to neurodegeneration.
Function
The HSP70 family of proteins constitutes a highly conserved group of molecular chaperones that play critical roles in protein homeostasis, folding, and quality control within cells[@mayer2005]. These proteins utilize ATP-dependent mechanisms to facilitate the refolding of misfolded proteins, prevent protein aggregation, and assist in the translocation of polypeptides across cellular membranes[@rosenzweig2019].
In [neurons](/entities/neurons), HSP70 proteins are particularly important for maintaining proteostasis under conditions of cellular stress, including oxidative stress, mitochondrial dysfunction, and proteasomal impairment — all hallmarks of neurodegenerative diseases[@turturici2014]. HSP70 interacts with co-chaperones from the DnaJ (HSP40) family and the BAG (Bcl-2-associated athanogene) family to regulate its ATPase activity and substrate targeting[@kampinga2010].
Disease Associations
Alzheimer's Disease
HSP70 has been shown to protect against [amyloid-beta](/proteins/amyloid-beta) toxicity in cellular and animal models of Alzheimer's disease[@hoshino2011]. The protein can:
- Reduce amyloid-beta aggregation and plaque formation
- Promote clearance of toxic oligomers via [autophagy](/entities/autophagy)
- Protect synaptic function and memory consolidation
Parkinson's Disease
In Parkinson's disease, HSP70 protects against [alpha-synuclein](/proteins/alpha-synuclein) toxicity by[@zhou2021]:
- Preventing alpha-synuclein fibrillation
- Targeting damaged proteins for degradation
- Protecting dopaminergic neurons from cell death
Amyotrophic Lateral Sclerosis (ALS)
HSP70 mutations are associated with ALS risk, and the protein has been shown to protect against [TDP-43](/mechanisms/tdp-43-proteinopathy) and SOD1 toxicity[@chen2023].
Expression
HSP70 is constitutively expressed at low levels in most tissues, including the brain, with particularly high expression in:
- Hippocampal neurons
- Cerebral [cortex](/brain-regions/cortex)
- Substantia nigra dopaminergic neurons
Expression is dramatically upregulated in response to cellular stress including heat shock, oxidative stress, and proteotoxic insults[@sharp2014].
Therapeutic Implications
HSP70 inducers (e.g., geldanamycin derivatives, geranylgeranylacetone) are being explored as potential therapies for neurodegenerative diseases[@nakamura2022]. The goal is to boost endogenous protective mechanisms to clear toxic protein aggregates.
See Also
- [Alzheimer's Disease](/diseases/alzheimers-disease)
- [Parkinson's Disease](/diseases/parkinsons-disease)
External Links
- [PubMed](https://pubmed.ncbi.nlm.nih.gov/)
- [KEGG Pathways](https://www.genome.jp/kegg/pathway.html)
Allen Brain Atlas Resources
- [Allen Human Brain Atlas - HSP70 Expression](https://human.brain-map.org/microarray/search/show?search_term=HSP70): Gene expression data in human brain
- [Allen Mouse Brain Atlas - Hsp70](https://mouse.brain-map.org/search?type=gene&term=Hsp70): Expression in mouse brain
- [BrainSpan Atlas - HSP70](https://brainspan.org/search?query=HSP70): Developmental expression data
References
[Mayer MP, Bukau B, Hsp70 chaperones: cellular functions and molecular mechanism (2005)](https://pubmed.ncbi.nlm.nih.gov/15770469/)
[Rosenzweig R, Nillegoda NB, Mayer MP, Bukau B, The Hsp70 chaperone network (2019)](https://doi.org/10.1038/s41580-019-0133-3)
[Turturici G, Tinnirello R, Sconzo G, Geraci F, Heat shock proteins and brain pathologies (2014)](https://pubmed.ncbi.nlm.nih.gov/24631079/)
[Kampinga HH, Craig EA, The HSP70 chaperone machinery: J-proteins as HSP70 co-chaperones (2010)](https://doi.org/10.1038/nrm2941)
[Hoshino T, Murao N, Namba T, et al, Suppression of Alzheimer's disease-related phenotypes by geranylgeranylacetone in mice (2011)](https://doi.org/10.1371/journal.pone.0021771)
[Zhou Y, Gu G, Goodyer AG, et al, Molecular and cellular evidence for the therapeutic role of Hsp70 in Parkinson's disease (2021)](https://doi.org/10.1111/jnc.15184)
[Chen HJ, Mitchell NC, Esser M, et al, Hsp70 and its cochaperone Hsp40 modify the ALS phenotype and protect against mutant SOD1 toxicity (2023)](https://doi.org/10.1093/brain/awad040)
[Sharp FR, Zhan X, Liu DZ, Heat shock proteins in the brain: role in neuroprotection and as therapeutic targets (2014)](https://doi.org/10.1111/jnc.12493)
[Nakamura J, Fujimoto Y, Takeda S, et al, Hsp90 inhibitors: potential therapeutic agents for neurodegenerative diseases (2022)](https://doi.org/10.1016/j.brainresbull.2022.01.012)From the [SciDEX Exchange](/exchange) — scored by multi-agent debate
- [Proteostasis Enhancement via APOE Chaperone Targeting](/hypothesis/h-5d943bfc) — <span style="color:#81c784;font-weight:600">0.70</span> · Target: HSPA1A
Pathway Diagram
The following diagram shows the key molecular relationships involving HSP70 Gene discovered through SciDEX knowledge graph analysis:
Mermaid diagram (expand to render)