Heat Shock Proteins and Protection of the Nervous System

  title={Heat Shock Proteins and Protection of the Nervous System},
  author={Ian R Brown},
  journal={Annals of the New York Academy of Sciences},
  • I. Brown
  • Published 1 October 2007
  • Biology
  • Annals of the New York Academy of Sciences
Abstract:  Manipulation of the cellular stress response offers strategies to protect brain cells from damage induced by ischemia and neurodegenerative diseases. Overexpression of Hsp70 reduced ischemic injury in the mammalian brain. Investigation of the domains within Hsp70 that confers ischemic neuroprotection revealed the importance of the carboxyl‐terminal domain. Arimoclomol, a coinducer of heat shock proteins, delayed progression of amyotrophic lateral sclerosis (ALS) in a mouse model in… 
Heat Shock Protein 70 (HSP70) Induction: Chaperonotherapy for Neuroprotection after Brain Injury
The neuroprotective mechanisms of HSP70 are summarized and potential ways in which this endogenous therapeutic molecule could be practically induced by pharmacological means to ultimately improve neurological outcomes in acute neurological disease are discussed.
Role of Heat Shock Proteins (HSP) in Neuroprotection for Ischemic Stroke
HSP seem to be neuroprotective, and should be further explored as a potential therapy against stroke and other neurodegenerative diseases.
Neuroprotection of Heat Shock Proteins (HSPs) in Brain Ischemia
HSPs should be further investigated for their translational relevance in the treatment of stroke and related conditions and the availability of a few pharmacological inducers has shown that this same neuroprotective effect can be recapitulated in wildtype animal models.
Localization of heat shock proteins in cerebral cortical cultures following induction by celastrol
Celastrol is a potential agent to counter this neurodegenerative disorder as recent evidence indicates that in vivo administration of celastrol in a transgenic model of Alzheimer’s reduces an important neuropathological hallmark of this disease, namely, amyloid beta pathology that involves protein aggregation.
The Role of HSPA12B in Regulating Neuronal Apoptosis
Results suggested that HSPA12B may be required for protecting neurons from ischemic insult processes in adult rats.
Role of Heat Shock Protein 90 in the Cause of Various Diseases: A Potential Therapeutic Target
In conclusion, inhibition of HSP90 has been found to be a novel strategy to target such diseases and pave the novel way of battling with these lethal diseases.
The role of heat shock proteins in spinal cord injury.
Heat shock proteins are normal intracellular proteins that are produced in greater amounts when cells are subjected to stress or injury and can also be liberated into the systemic circulation to act as important inflammatory mediators.


Induction of heat shock proteins in differentiated human and rodent neurons by celastrol
Celastrol, a quinine methide triterpene, induced expression of a wider set of Hsps, including Hsp70B′, in differentiated human neurons grown in tissue culture compared to cultured rodent neuronal cells, suggesting that the beneficial effect of celastrol against human neurodegenerative diseases may exceed its potential in rodent models of these diseases.
Antiapoptotic and Anti‐inflammatory Mechanisms of Heat‐Shock Protein Protection
It is suggested that HSPs are capable of protecting brain cells from lethal insults through a variety of mechanisms and should be explored as a potential therapy against stroke and other neurodegenerative diseases.
Administration of Hsp70 in vivo inhibits motor and sensory neuron degeneration
It appears that motor and sensory neurons in the neonatal mouse do not initiate a typical Hsp70 response after traumatic injury and that administration of exogenous Hsc/Hsp70 can remedy that deficit and reduce the subsequent loss of neurons by apoptosis.
High Threshold for Induction of the Stress Response in Motor Neurons Is Associated with Failure to Activate HSF1
The results indicate that the high threshold for induction of the stress response in motor neurons stems from an impaired ability to activate the main heat shock–stress sensor, HSF1.
Chaperones, protein aggregation, and brain protection from hypoxic/ischemic injury
It is demonstrated that overexpression of Hsp70 in hippocampal CA1 neurons reduces evidence of protein aggregation under conditions where neuronal survival is increased, and protection by the cochaperone Hdj-2 in vitro and this is associated with reduced protein aggregation identified by ubiquitin immunostaining.
Translocation of constitutively expressed heat shock protein Hsc70 to synapse‐enriched areas of the cerebral cortex after hyperthermic stress
The results suggest that the heat shock response in the nervous system involves not only the synthesis of stress‐inducible Hsps but also the translocation of constitutively expressed Hsc70 to synapse‐enriched areas where it could participate in neuroprotective mechanisms that preserved synaptic function during times of stress.
Mice overexpressing rat heat shock protein 70 are protected against cerebral infarction
It is suggested that HSP70 can markedly protect the brain against ischemic damage and that approaches aimed at inducing HSP 70 may lead to new therapeutic interventions in cerebrovascular injuries.
Exogenous heat shock cognate protein Hsc 70 prevents axotomy-induced death of spinal sensory neurons.
Application of exogenous Hsc70 prevented axotomy-induced death of virtually all sensory neurons, but did not significantly alter motoneuron death, suggesting that HSc70 may prove to be useful in the repair of peripheral sensory nerve damage.
Extracellular Heat Shock Protein 70: A Critical Component for Motoneuron Survival
It is demonstrated that, although endogenous expression of heat shock protein 70 (HSP70) did not change during trophic factor deprivation, application of e-rhHsp70 (exogenous recombinant human Hsp70) promoted motoneuron survival and indicated that the source of this factor is instrumental in determining its trophics function.