Induction of heat shock proteins in differentiated human neuronal cells following co-application of celastrol and arimoclomol

Deane, Catherine A. S.; Brown, Ian R.

doi:10.1007/s12192-016-0708-2

Cited by 41 publications

(32 citation statements)

References 94 publications

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“…Induced Hsps are involved in nascent protein folding and the prevention of protein aggregation [14]. In brain cells, heat stress triggers a robust expression of induced Hsps, such as Hsp70, Hsp32, and Hsp27 [15]. Hsp70 has been the most widely studied in terms of its neuroprotective properties.…”

Section: Heat Shock Protein 70mentioning

confidence: 99%

The 70-kDa heat shock protein (Hsp70) as a therapeutic target for stroke

Kim

Han

Lee

et al. 2018

Expert Opinion on Therapeutic Targets

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Introduction: The 70-kDa heat shock protein (Hsp70) is a cytosolic chaperone which facilitates protein folding, degradation, complex assembly, and translocation. Following stroke, these functions have the potential to lead to cytoprotection, and this has been demonstrated using genetic mutant models, direct gene transfer or the induction of Hsp70 via heat stress, approaches which limit its translational utility. Recently, the investigation of Hsp70-inducing pharmacological compounds, which, through their ability to inhibit Hsp90, has obvious clinical implications in terms of potential therapies to mitigate cell death and inflammation, and lead to neuroprotection from brain injury. Areas covered: In this review, we will focus on the role of Hsp70 in cell death and inflammation, and the current literature surrounding the pharmacological induction in acute ischemic stroke models with comments on potential applications at the clinical level. Expert opinion: Such neuroprotectants could be used to synergistically improve neurological outcome or to extend the time window of existing interventions, thus increasing the numbers of stroke victims eligible for treatment.

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Section: Heat Shock Protein 70mentioning

confidence: 99%

The 70-kDa heat shock protein (Hsp70) as a therapeutic target for stroke

Kim

Han

Lee

et al. 2018

Expert Opinion on Therapeutic Targets

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“…Resveratrol, Celastrol and Arimoclomol are 3 compounds that have been reported to delay disease onset and extend survival in SOD1(G93A) transgenic mice (75–77). Each of these compounds indirectly activate heat shock factor 1, the master regulator of HSP gene transcription, and in vitro studies demonstrate that they can increase HSPB1 expression (75, 78, 79). Each of these treatments hold promise, yet the effect these compounds have on HSP regulation in non-neuronal cells has been poorly characterized.…”

Section: Discussionmentioning

confidence: 99%

HSPB1 mutations causing hereditary neuropathy in humans disrupt non-cell autonomous protection of motor neurons

Heilman

Song

Miranda

et al. 2017

Experimental Neurology

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Heat shock protein beta-1 (HSPB1), is a ubiquitously expressed, multifunctional protein chaperone. Mutations in HSPB1 result in the development of a late-onset, distal hereditary motor neuropathy type II (dHMN) and axonal Charcot-Marie Tooth disease with sensory involvement (CMT2F). The functional consequences of HSPB1 mutations associated with hereditary neuropathy are unknown. HSPB1 also displays neuroprotective properties in many neuronal disease models, including the motor neuron disease amyotrophic lateral sclerosis (ALS). HSPB1 is upregulated in SOD1-ALS animal models during disease progression, predominately in glial cells. Glial cells are known to contribute to motor neuron loss in ALS through a non-cell autonomous mechanism. In this study, we examined the non-cell autonomous role of wild type and mutant HSPB1 in an astrocyte-motor neuron co-culture model system of ALS. Astrocyte-specific overexpression of wild type HSPB1 was sufficient to attenuate SOD1(G93A) astrocyte-mediated toxicity in motor neurons, whereas, overexpression of mutHSPB1 failed to ameliorate motor neuron toxicity. Expression of a phosphomimetic HSPB1 mutant in SOD1(G93A) astrocytes also reduced toxicity to motor neurons, suggesting that phosphorylation may contribute to HSPB1 mediated-neuroprotection. These data provide evidence that astrocytic HSPB1 expression may play a central role in motor neuron health and maintenance.

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“…In the present study, live imaging and FRAP were utilized to further knowledge of HSPA6 (Hsp70B'), a little studied member of the HSPA (Hsp70) multigene family that is present in the human genome but absent in the genomes of mouse and rat (Chow and Brown 2007;Noonan et al 2007a;Noonan et al 2007b;Noonan et al 2008a;Noonan et al 2008b;Chow et al 2010;Ramirez et al 2015;Deane and Brown 2016). Following thermal stress, changes in the intracellular localization of HSPA6, and the more widely studied HSPA1A (Hsp70-1), were visualized in living differentiated human neuronal SH-SY5Y cells, with FRAP employed to compare the dynamics of the exchange of these two Hsps with stresssensitive cytoplasmic and nuclear structures.…”

Section: Discussionmentioning

confidence: 99%

“…Heat shock proteins (Hsps) are cellular repair agents that counter the effects of protein misfolding, and their upregulation has been proposed as a potential strategy to counter neurodegenerative disorders (Muchowski and Wacker 2005;Asea and Brown 2008;Pratt et al 2015). The HSPA (Hsp70) family has been widely studied, particularly HSPA1A (Hsp70-1), however HSPA6 (Hsp70B') has received comparatively little attention (Chow and Brown 2007;Noonan et al 2007a;Noonan et al 2007b;Noonan et al 2008a;Noonan et al 2008b;Chow et al 2010;Ramirez et al 2015;Deane and Brown 2016). Interestingly, HSPA6 is present in the human genome and absent in the genomes of mouse and rat.…”

Section: Introductionmentioning

confidence: 99%

Dynamics of the association of heat shock protein HSPA6 (Hsp70B’) and HSPA1A (Hsp70–1) with stress-sensitive cytoplasmic and nuclear structures in differentiated human neuronal cells

Shorbagi

Brown

2016

Cell Stress and Chaperones

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Heat shock proteins (Hsps) are cellular repair agents that counter the effects of protein misfolding that is a characteristic feature of neurodegenerative diseases. HSPA1A (Hsp70-1) is a widely studied member of the HSPA (Hsp70) family. The little-studied HSPA6 (Hsp70B') is present in the human genome and absent in mouse and rat; hence, it is missing in current animal models of neurodegenerative diseases. Differentiated human neuronal SH-SY5Y cells were employed to compare the dynamics of the association of YFP-tagged HSPA6 and HSPA1A with stress-sensitive cytoplasmic and nuclear structures. Following thermal stress, liveimaging confocal microscopy and Fluorescence Recovery After Photobleaching (FRAP) demonstrated that HSPA6 displayed a prolonged and more dynamic association, compared to HSPA1A, with centrioles that play critical roles in neuronal polarity and migration. HSPA6 and HSPA1A also targeted nuclear speckles, rich in RNA splicing factors, and the granular component of the nucleolus that is involved in rRNA processing and ribosomal subunit assembly. HSPA6 and HSPA1A displayed similar FRAP kinetics in their interaction with nuclear speckles and the nucleolus. Subsequently, during the recovery from neuronal stress, HSPA6, but not HSPA1A, localized with the periphery of nuclear speckles (perispeckles) that have been characterized as transcription sites. The stress-induced association of HSPA6 with perispeckles displayed the greatest dynamism compared to the interaction of HSPA6 or HSPA1A with other stresssensitive cytoplasmic and nuclear structures. This suggests involvement of HSPA6 in transcriptional recovery of human neurons from cellular stress that is not apparent for HSPA1A.

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Induction of heat shock proteins in differentiated human neuronal cells following co-application of celastrol and arimoclomol

Cited by 41 publications

References 94 publications

The 70-kDa heat shock protein (Hsp70) as a therapeutic target for stroke

The 70-kDa heat shock protein (Hsp70) as a therapeutic target for stroke

HSPB1 mutations causing hereditary neuropathy in humans disrupt non-cell autonomous protection of motor neurons

Dynamics of the association of heat shock protein HSPA6 (Hsp70B’) and HSPA1A (Hsp70–1) with stress-sensitive cytoplasmic and nuclear structures in differentiated human neuronal cells

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