Putting the heat on ALS

  title={Putting the heat on ALS},
  author={Susanna C. Benn and Robert H. Brown},
  journal={Nature Medicine},
An enhancer of the heat shock response alleviates symptoms of neurodegeneration and prolongs lifespan in a mouse model of amyotrophic lateral sclerosis—even when administered after onset (pages 402–405). 
Complex genetics of amyotrophic lateral sclerosis.
  • C. B. Kunst
  • Medicine
    American journal of human genetics
  • 2004
This work was supported by National Institutes of Health grant NS041646, and the authors thank Dr. Patrick Bosque, Dr. Miles Brennan, and Sharon Trilk for helpful comments and corrections.
Heat Shock Proteins and Protection of the Nervous System
  • I. Brown
  • Biology
    Annals of the New York Academy of Sciences
  • 2007
Application of exogenous Hsps at neural injury sites is an effective strategy to maintain neuronal viability and Manipulation of the cellular stress response offers strategies to protect brain cells from damage induced by ischemia and neurodegenerative diseases.
Heat Shock Protein 70: Roles in Multiple Sclerosis
The functions of HSP are dissected, controversial data concerning the role of Hsp70 in MS and EAE are discussed and the most relevant HSP is the inducible HSP70, which exhibits both cytoprotectant and immunoregulatory functions.
Heat Shock Proteins and Neurodegenerative Diseases
This review explores the possibility that manipulation of the cellular stress response offers opportunities to counter conformational changes in proteins that trigger pathogenic cascades that result in neurodegenerative diseases.
Molecular Chaperones in Neurodegeneration
This chapter presents a generalized view of misfolding and aggregation of proteins in neurodegeneration and then critically analyses some of the known cellular chaperones and their role in several Neurodegenerative disorders.
The steady, inevitable decline of amyotrophic lateral sclerosis patients.
  • G. Zanni, J. Wick
  • Psychology, Biology
    The Consultant pharmacist : the journal of the American Society of Consultant Pharmacists
  • 2005
All ALS patients can be expected to progress to a state that requires complete supportive care, and the treatment and prognosis have been unchanged for almost 100 years, although the understanding on a cellular level is better.
Molecular chaperones biochemistry and role in neurodegenerative diseases.
  • Ali Chaari
  • Biology
    International journal of biological macromolecules
  • 2019
Significance of heat shock proteins in the skin upon UV exposure.
The expression of heat shock proteins (Hsp) expression is induced in all cells by exposure to heat and other environmental stress and Hsp can protect cells from damage through further exposure and can be inhibited by previous heat shock and UV itself can induce Hsp experimentally.
Molecular chaperones in Parkinson's disease--present and future.
The capacity of molecular chaperones to prevent or modulate neurodegeneration, an important concept for future neuroprotective strategies, is discussed and the current progress in preclinical studies in models of Parkinson's disease is summarized.
Changes in the regulation of heat shock gene expression in neuronal cell differentiation
This study shows that changes in regulation of the HSP and HSC proteins are components of the neuronal cell differentiation program and that the attenuated induction of HSPs likely contributes to neuronal vulnerability whereas the increased expression of Hsc70 likely has a role in neural-specific functions.


Pharmacological modulation of heat shock factor 1 by antiinflammatory drugs results in protection against stress-induced cellular damage.
It is shown that the potent antiinflammatory drug indomethacin activates the DNA-binding activity of human heat shock transcription factor 1 (HSF1), such that a complete heat shock response can be attained at temperatures that are by themselves insufficient.
Treatment with arimoclomol, a coinducer of heat shock proteins, delays disease progression in ALS mice
Treatment with arimoclomol, a coinducer of heat shock proteins (HSPs), significantly delays disease progression in mice expressing a SOD1 mutant in which glycine is substituted with alanine at position 93 (SOD1G93A).
Up‐Regulation of Protein Chaperones Preserves Viability of Cells Expressing Toxic Cu/Zn‐Superoxide Dismutase Mutants Associated with Amyotrophic Lateral Sclerosis
Evidence is presented that mutations in the Cu/Zn‐superoxidedismutase (SOD‐1) gene underlie some familial cases of amytotrophic lateral sclerosis, a neurodegenerative disorder charactreized by loss of cortical, brainstem, and spinal motor nrurons, and that insufficiency of molecular chaperones may be directly involved in loss of motor neurons in this disease.
Upregulation of Heat Shock Proteins Rescues Motoneurones from Axotomy-Induced Cell Death in Neonatal Rats
Treatment with BRX-220, a co-inducer of hsps, protects motoneurones from axotomy-induced cell death and results in a significant increase in the expression of hsp70 and hsp90 in glia and neurones.
Carbenoxolone, a new inducer of heat shock protein 70.
Amyotrophic lateral sclerosis: A proposed mechanism
It is demonstrated that the entry of SOD1 into mitochondria depends on demetallation and that heat shock proteins block the uptake of the FALS-associated mutant S OD1 (G37R, G41D, or G93A), while having no effect on wild-type SOD 1.
Wild-Type Nonneuronal Cells Extend Survival of SOD1 Mutant Motor Neurons in ALS Mice
Nonneuronal cells that do not express mutant SOD1 delay degeneration and significantly extend survival of mutant-expressing motor neurons.