Molecular chaperones as therapeutic targets in amyotrophic lateral sclerosis

2005 ◽  
Vol 33 (4) ◽  
pp. 551-552 ◽  
Author(s):  
B. Kalmar ◽  
D. Kieran ◽  
L. Greensmith
Keyword(s):  
Cell Death ◽  
Amyotrophic Lateral Sclerosis ◽  
Heat Shock ◽  
Molecular Chaperones ◽  
Apoptotic Cell ◽  
Structural Repair ◽  
Cell Death Pathway ◽  
Shock Proteins ◽  
Intracellular Aggregates ◽  
Lateral Sclerosis

Neurodegenerative diseases are characterized by a number of common hallmarks, such as the presence of intracellular aggregates and activation of the apoptotic cell-death pathway. Intracellular chaperones, responsible for protein integrity and structural repair, may play a crucial role in the progression of a disease. In this paper, we aim to summarize our understanding of the role and potential of a particular family of chaperones, the heat-shock proteins, in neurodegeneration, by focusing our discussion on models of motoneuron death.

scholarly journals Activation of the heat shock response in a primary cellular model of motoneuron neurodegeneration-evidence for neuroprotective and neurotoxic effects

2009 ◽  
Vol 14 (2) ◽  
Author(s):  
Bernadett Kalmar ◽  
Linda Greensmith
Keyword(s):  
Cell Death ◽  
Heat Shock ◽  
Heat Shock Response ◽  
Apoptotic Cell ◽  
Experimental Conditions ◽  
Pharmacological Agents ◽  
Shock Response ◽  
Induced Apoptosis ◽  
Shock Proteins ◽  
The Relationship

AbstractPharmacological up-regulation of heat shock proteins (hsps) rescues motoneurons from cell death in a mouse model of amyotrophic lateral sclerosis. However, the relationship between increased hsp expression and neuronal survival is not straightforward. Here we examined the effects of two pharmacological agents that induce the heat shock response via activation of HSF-1, on stressed primary motoneurons in culture. Although both arimoclomol and celastrol induced the expression of Hsp70, their effects on primary motoneurons in culture were significantly different. Whereas arimoclomol had survival-promoting effects, rescuing motoneurons from staurosporin and H2O2 induced apoptosis, celastrol not only failed to protect stressed motoneurons from apoptosis under same experimental conditions, but was neurotoxic and induced neuronal death. Immunostaining of celastrol-treated cultures for hsp70 and activated caspase-3 revealed that celastrol treatment activates both the heat shock response and the apoptotic cell death cascade. These results indicate that not all agents that activate the heat shock response will necessarily be neuroprotective.

scholarly journals Necrotic but not apoptotic cell death releases heat shock proteins, which deliver a partial maturation signal to dendritic cells and activate the NF-κB pathway

2000 ◽  
Vol 12 (11) ◽  
pp. 1539-1546 ◽  
Author(s):  
Sreyashi Basu ◽  
Robert J. Binder ◽  
Ryuichiro Suto ◽  
Kirstin M. Anderson ◽  
Pramod K. Srivastava
Keyword(s):  
Cell Death ◽  
Dendritic Cells ◽  
Heat Shock ◽  
Heat Shock Proteins ◽  
Apoptotic Cell ◽  
Apoptotic Cell Death ◽  
Shock Proteins

Heat Shock Proteins: Endogenous Modulators of Apoptotic Cell Death

2001 ◽  
Vol 286 (3) ◽  
pp. 433-442 ◽  
Author(s):  
Carmen Garrido ◽  
Sandeep Gurbuxani ◽  
Luigi Ravagnan ◽  
Guido Kroemer
Keyword(s):  
Cell Death ◽  
Heat Shock ◽  
Heat Shock Proteins ◽  
Apoptotic Cell ◽  
Apoptotic Cell Death ◽  
Shock Proteins ◽  
Endogenous Modulators

scholarly journals SECOND ANOXIA-REOXYGENATION DOES NOT CAUSE THE APOPTOTIC CELL DEATH OF NEONATAL CARDIOMYOCYTES: POSSIBLE ROLE OF CHANGES OF mRNA EXPRESSION OF CYTOPROTECTIVE GENES

2009 ◽  
Vol 55 (1) ◽  
pp. 19-26
Author(s):  
O.V. Surova ◽  
◽  
V.E. Dosenko ◽  
V.S. Nagibin ◽  
L.V. Tumanovskaya ◽  
...  
Keyword(s):  
Cell Death ◽  
Heat Shock ◽  
Heat Shock Proteins ◽  
Apoptotic Cell ◽  
First Episode ◽  
Mrna Levels ◽  
Neonatal Cardiomyocytes ◽  
Genes Expression ◽  
Shock Proteins

The cells death and genes expression in neonatal cardiomyocytes culture at two anoxia-reoxygenation modeling were investigated. The primary culture of neonatal cardiomyocytes was under­gone 30 min of anoxia followed by 24 h (A-R1) and the second anoxia-reoxygenation – 30 min and 60 min respectively (A-R2). The percentages of living, necrotic, apoptotic and autophagic cells were determined by staining with bis-benzimide, propidium iodide and monodansylcadaverine. Anoxia-reoxygenation sig­nificantly influenced the ratio of living, necrotic, apoptotic and autophagic cells both at its first A-R1 and second A-R2 epi­sodes. It was shown that the main mechanism of cell death after the both periods of anoxia-reoxygenation is necrosis. The changes of mRNA levels of genes of heat shock proteins HSP70 and HSP90, antiapoptotic protein Bcl2 and key regulator of au-tophagy FRAP in cardiomyocytes culture were established. The data obtained allow to make suggestion that in 24 h after the first episode of anoxia-reoxygenation A-R1 the overexpression of heat shock proteins starts the cascade of reactions that causes the necrotic cell death prevalent and the blocking of apoptotic program at second anoxia-reoxygenation A-R2.

Apoptotic Cell Death of a Hybrid Motoneuron Cell Line Induced by Immunoglobulins from Patients with Amyotrophic Lateral Sclerosis

2002 ◽  
Vol 63 (6) ◽  
pp. 2365-2368 ◽  
Author(s):  
Maria E. Alexianu ◽  
A. Habib Mohamed ◽  
R. Glenn Smith ◽  
Luis V. Colom ◽  
Stanley H. Appel
Keyword(s):  
Cell Death ◽  
Amyotrophic Lateral Sclerosis ◽  
Cell Line ◽  
Apoptotic Cell ◽  
Apoptotic Cell Death ◽  
Motoneuron Cell ◽  
Lateral Sclerosis

Chaperoning signaling pathways: molecular chaperones as stress-sensing`heat shock' proteins

2002 ◽  
Vol 115 (14) ◽  
pp. 2809-2816 ◽  
Author(s):  
Ellen A. A. Nollen ◽  
Richard I. Morimoto
Keyword(s):  
Cell Death ◽  
Heat Shock ◽  
Heat Shock Proteins ◽  
Signaling Pathways ◽  
Molecular Chaperones ◽  
Growth Control ◽  
Normal Function ◽  
Stress Sensing ◽  
As Stress ◽  
Shock Proteins

Heat shock proteins interact with multiple key components of signaling pathways that regulate growth and development. The molecular relationships between heat shock proteins, various signaling proteins and partner proteins appear to be critical for the normal function of signal transduction pathways. The relative levels of these proteins may be important, as too little or too much Hsp70 or Hsp90 can result in aberrant growth control, developmental malformations and cell death. Although the functions of heat shock proteins as molecular chaperones have been well characterized, their complementary role as a `stress-induced' proteins to monitor changes and alter the biochemical environment of the cell remains elusive. Genetic and molecular interactions between heat shock proteins, their co-chaperones and components of signaling pathways suggest that crosstalk between these proteins can regulate proliferation and development by preventing or enhancing cell growth and cell death as the levels of heat shock proteins vary in response to environmental stress or disease.

Induction of multiple heat shock proteins and neuroprotection in a primary culture model of familial amyotrophic lateral sclerosis

2006 ◽  
Vol 24 (2) ◽  
pp. 213-225 ◽  
Author(s):  
Zarah Batulan ◽  
David M. Taylor ◽  
Rebecca J. Aarons ◽  
Sandra Minotti ◽  
Mohammad M. Doroudchi ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Heat Shock ◽  
Heat Shock Proteins ◽  
Primary Culture ◽  
Familial Amyotrophic Lateral Sclerosis ◽  
Culture Model ◽  
Shock Proteins ◽  
Lateral Sclerosis
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