Localization of heat shock proteins in cerebral cortical cultures following induction by celastrol

Chow, Ari M.; Tang, Derek W. F.; Hanif, Asad; Brown, Ian R.

doi:10.1007/s12192-014-0508-5

Cited by 18 publications

(10 citation statements)

References 34 publications

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“…Brown and associates recently reported in this journal the potential for celastrol as a viable therapy for neurodegenerative disease (Chow et al 2014). Their study emphasized the ability of HSP induction by celastrol to protect the brain from misfolded, aggregation-prone proteins in diseases like Alzheimer's.…”

Section: Hsf1 Inducers and Cognitive Preservationmentioning

confidence: 99%

The central role of heat shock factor 1 in synaptic fidelity and memory consolidation

Hooper

Durham

Török

et al. 2016

Cell Stress and Chaperones

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Networks of neuronal synapses are the fundamental basis for making and retaining memory. Reduced synapse number and quality correlates with loss of memory in dementia. Heat shock factor 1 (HSF1), the major transcription factor regulating expression of heat shock genes, plays a central role in proteostasis, in establishing and sustaining synaptic fidelity and function, and in memory consolidation. Support for this thesis is based on these observations: (1) heat shock induces improvements in synapse integrity and memory consolidation; (2) synaptic depolarization activates HSF1; (3) activation of HSF1 alone (independent of the canonical heat shock response) augments formation of essential synaptic elementsneuroligands, vesicle transport, synaptic scaffolding proteins, lipid rafts, synaptic spines, and axodendritic synapses; (4) HSF1 coalesces and activates memory receptors in the postsynaptic dendritic spine; (5) huntingtin or α-synuclein accumulation lowers HSF1 while HSF1 lowers huntingtin and α-synuclein aggregation-a potential vicious cycle; and (6) HSF1 agonists (including physical activity) can improve cognitive function in dementia models. Thus, via direct gene expression of synaptic elements, production of HSPs that assure high protein fidelity, and activation of other neuroprotective signaling pathways, HSF1 agonists could provide breakthrough therapy for dementia-associated disease.

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Section: Hsf1 Inducers and Cognitive Preservationmentioning

confidence: 99%

The central role of heat shock factor 1 in synaptic fidelity and memory consolidation

Hooper

Durham

Török

et al. 2016

Cell Stress and Chaperones

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“…Although activated Hsp27 positive astrocytes were located in close proximity of degenerating neurons, we found very rare colocalization of Hsp27 with specific markers of degenerated neurons. It was published that Hsp27 is expressed in astrocytes and oligodendroglia in tauopathies with extensive glial pathology [13,22,23,33], however in our model there is no expression of pathological tau in astrocytes and other glial cells. The pathological tau in the rat transgenic model is expressed exclusively in neurons (driven by Thy1 promoter).…”

Section: Discussionmentioning

confidence: 62%

“…The up-regulation of small molecular weight heat shock protein (Hsp27) has been detected in both neurons and astrocytes of different animal species under stress and in neurodegenerative conditions [2,14,17,22,23,27,33,57]. The elevated levels of Hsp27 in the cortex of brains from AD patients were revealed by immunohistochemical and biochemical studies.…”

Section: Introductionmentioning

confidence: 99%

Intraneuronal accumulation of misfolded tau protein induces overexpression of Hsp27 in activated astrocytes

Filipčík¹,

Cente²,

Žilka³

et al. 2015

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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Accumulation of misfolded forms of microtubule associated, neuronal protein tau causes neurofibrillary degeneration typical of Alzheimer's disease and other tauopathies. This process is accompanied by elevated cellular stress and concomitant deregulation of heat-shock proteins. We used a transgenic rat model of tauopathy to study involvement of heat shock protein 27 (Hsp27) in the process of neurofibrillary degeneration, its cell type specific expression and correlation with the amount of insoluble tau protein aggregates. The expression of Hsp27-mRNA is more than doubled and levels of Hsp27 protein tripled in aged transgenic animals with tau pathology. The data revealed a strong positive and highly significant correlation between Hsp27-mRNA and amount of sarkosyl insoluble tau. Interestingly, intracellular accumulation of insoluble misfolded tau protein in neurons was associated with overexpression of Hsp27 almost exclusively in reactive astrocytes, not in neurons. The topological dissociation of neuronally expressed pathological tau and the induction of astrocytic Hsp27, GFAP, and Vimentin along with up-regulation of microglia specific markers such as CD18, CD68 and C3 point to cooperation of astrocytes, microglia and neurons in response to intra-neuronal accumulation of insoluble tau. Our data suggest that over expression of Hsp27 represents a part of microglia-mediated astrocytic response mechanism in the process of neurofibrillary degeneration, which is not necessarily associated with neuroprotection and which in contrary may accelerate neurodegeneration in late stage of the disease. This phenomenon should be considered during development of disease modifying strategies for treatment of tauopathies and AD via regulation of activity of Hsp27.

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“…Celastrol increased HSP70 while mitigated iNOS, TNF, cluster of differentiation 40 (CD40), and GFAP proteins expression in the lumbar spinal cord of G93A mice [288]. Celastrol effects on HSPs have also been reported to play a key neuroprotective role in defense against misfolded proteins and aggregation-prone proteins [289]. Speaking of protein aggregation, celastrol was reported to inhibit amyloid beta aggregation, the main toxin to be accounted for AD initiation and progression [276,281].…”

Section: Celastrolmentioning

confidence: 99%

Terpenoids, Cannabimimetic Ligands, beyond the Cannabis Plant

et al. 2020

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Medicinal use of Cannabis sativa L. has an extensive history and it was essential in the discovery of phytocannabinoids, including the Cannabis major psychoactive compound—Δ9-tetrahydrocannabinol (Δ9-THC)—as well as the G-protein-coupled cannabinoid receptors (CBR), named cannabinoid receptor type-1 (CB1R) and cannabinoid receptor type-2 (CB2R), both part of the now known endocannabinoid system (ECS). Cannabinoids is a vast term that defines several compounds that have been characterized in three categories: (i) endogenous, (ii) synthetic, and (iii) phytocannabinoids, and are able to modulate the CBR and ECS. Particularly, phytocannabinoids are natural terpenoids or phenolic compounds derived from Cannabis sativa. However, these terpenoids and phenolic compounds can also be derived from other plants (non-cannabinoids) and still induce cannabinoid-like properties. Cannabimimetic ligands, beyond the Cannabis plant, can act as CBR agonists or antagonists, or ECS enzyme inhibitors, besides being able of playing a role in immune-mediated inflammatory and infectious diseases, neuroinflammatory, neurological, and neurodegenerative diseases, as well as in cancer, and autoimmunity by itself. In this review, we summarize and critically highlight past, present, and future progress on the understanding of the role of cannabinoid-like molecules, mainly terpenes, as prospective therapeutics for different pathological conditions.

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Localization of heat shock proteins in cerebral cortical cultures following induction by celastrol

Cited by 18 publications

References 34 publications

The central role of heat shock factor 1 in synaptic fidelity and memory consolidation

The central role of heat shock factor 1 in synaptic fidelity and memory consolidation

Intraneuronal accumulation of misfolded tau protein induces overexpression of Hsp27 in activated astrocytes

Terpenoids, Cannabimimetic Ligands, beyond the Cannabis Plant

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