The role of heat shock proteins Hsp70 and Hsp27 in cellular protection of the central nervous system

Franklin, Tamara B.; Am, Krueger-Naug; Clarke, Damian; Ap, Arrigo; Currie, R. William

doi:10.1080/02656730500069955

Cited by 192 publications

(119 citation statements)

References 73 publications

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“…1 The induction of Hsp70 production in the brain and retina is associated with cellular resistance to various types of damage. 9,32,33 Gadd34 and Hsp70 mRNA levels returned to basal values 24 hours after ischemia, but a second larger peak was observed for PAI1 mRNA. In accordance with our results, Docagne and colleagues 34 reported greater PAI1 mRNA levels between 24 hours and 3 days after middle cerebral artery occlusion in mice.…”

Section: Discussionmentioning

confidence: 94%

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Novel Mouse Model of Monocular Amaurosis Fugax

Lelong

Bièche

Perez

et al. 2007

Stroke

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Background and Purpose-Retinal ischemia is a major cause of visual impairment and is associated with a high risk of subsequent ischemic stroke. The retina and its projections are easily accessible for experimental procedures and functional evaluation. We created and characterized a mouse model of global and transient retinal ischemia and provide a comprehensive chronologic profile of some genes that display altered expression during ischemia. Methods-Ischemia and reperfusion were assessed by observing flat-mounted retinas after systemic fluorescein injection.The temporal pattern of gene expression modulation was evaluated by quantitative reverse transcription-polymerase chain reaction from the occurrence of unilateral 30-minute pterygopalatine artery occlusion until 4 weeks after reperfusion. Electroretinograms evaluated functional sequelae 4 weeks after the ischemic episode and were correlated with histologic lesions. Results-This model is the first to reproduce the features of transient monocular amaurosis fugax resulting from ophthalmic artery occlusion. The histologic structure was roughly conserved, but functional lesions affected ganglion cells, inner nuclear layer cells, and photoreceptor cells. We observed an early and strong upregulation of c-fos, c-jun, Cox-2, Hsp70, and Gadd34 gene expression and a late decrease in Hsp70 transcript levels. Conclusions-A murine model of transient retinal ischemia was successfully developed that exhibited the characteristic upregulation of immediate-early genes and persistent functional deficits. The model should prove useful for investigating mechanisms of injury in genetically altered mice and for testing novel neuroprotective drugs. (Stroke.

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Section: Discussionmentioning

confidence: 94%

“…8 A molecular "chaperone," heat-shock protein (Hsp) 70, also functions as an important cytoprotectant against oxidative stress and apoptosis. 9 We also measured the expression levels of 2 control genes, Thy-1 and Rho. These genes encode protein markers specific for 2 types of retinal neurons: ganglion cells (Thy-1) and rod photoreceptors (Rho).…”

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confidence: 99%

Novel Mouse Model of Monocular Amaurosis Fugax

Lelong

Bièche

Perez

et al. 2007

Stroke

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“…name) cord [1][2][3] high [4] high [4] UP in neurons [5,6] generally UNCHANGED UP in Purkinje cell (NPD) [7,8] generally UP [9][10][11][12][13][14][15][16] extracellular in AD brain [17] strong [3,18] no [1,19] SOD-1:…”

Section: Introductionmentioning

confidence: 99%

Different anti-aggregation and pro-degradative functions of the members of the mammalian sHSP family in neurological disorders

Carra

Rusmini

Crippa

et al. 2013

Phil. Trans. R. Soc. B

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The family of the mammalian small heat-shock proteins consists of 10 members (sHSPs/HSPBs: HSPB1–HSPB10) that all share a highly conserved C-terminal alpha-crystallin domain, important for the modulation of both their structural and functional properties. HSPB proteins are biochemically classified as molecular chaperones and participate in protein quality control, preventing the aggregation of unfolded or misfolded proteins and/or assisting in their degradation. Thus, several members of the HSPB family have been suggested to be protective in a number of neurodegenerative and neuromuscular diseases that are characterized by protein misfolding. However, the pro-refolding, anti-aggregation or pro-degradative properties of the various members of the HSPB family differ largely, thereby influencing their efficacy and protective functions. Such diversity depends on several factors, including biochemical and physical properties of the unfolded/misfolded client, the expression levels and the subcellular localization of both the chaperone and the client proteins. Furthermore, although some HSPB members are inefficient at inhibiting protein aggregation, they can still exert neuroprotective effects by other, as yet unidentified, manners; e.g. by maintaining the proper cellular redox state or/and by preventing the activation of the apoptotic cascade. Here, we will focus our attention on how the differences in the activities of the HSPB proteins can influence neurodegenerative and neuromuscular disorders characterized by accumulation of aggregate-prone proteins. Understanding their mechanism of action may allow us to target a specific member in a specific cell type/disease for therapeutic purposes.

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“…Endogenous heat shock proteins (Hsps) exert neuroprotective activity in rodent models of Huntington's disease, Amyotrophic Lateral Sclerosis, and other cases of neuropathologies (Cummings et al 2001;Franklin et al 2005;Wacker et al 2009;Gifondorwa et al 2007). In a cellular model of AD, Hsp70 overexpression effectively protected neurons from accumulation of Аβ (Magrané et al 2004;Hoshino et al 2011).…”

Section: Introductionmentioning

confidence: 99%

Dynamics of endogenous Hsp70 synthesis in the brain of olfactory bulbectomized mice

Бобкова

Guzhova

Margulis

et al. 2013

Cell Stress and Chaperones

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Numerous epidemiological studies have established acute brain injury as one of the major risk factors for the Alzheimer's disease (AD). However, the lack of animal models of AD-like degeneration triggered by a defined injury hampered the development of adequate therapies. Here we report that the surgical damage of the olfactory bulbs triggers the development of several pathologies, including amyloid-β accumulation and strong decrease of neuron density in the cortex and hippocampus as well as significant disturbance of spatial memory. Characteristically, these harmful consequences of the olfactory bulbectomy (OBX) have a peculiar dynamics in time with maximal manifestation in periods of 1-1.5 months and 8 months after the surgery and, hence, exhibit biphasic pattern with almost complete recovery period taking place at 5-6 months after the operation. The quantitative determination of endogenous inducible form of Hsp70 in different brain areas of OBX mice demonstrated characteristic fluctuations of Hsp70 levels depending on the time after the operation and age of mice. Interestingly, maximal induction of Hsp70 synthesis in the hippocampus exhibits clear-cut coincidence with the recovery period in OBX animals. The observed correlation enables to suggest curing effect of Hsp70 synthesis at an earlier period of pathology development and establishes it as a possible therapeutic agent for secondary grave consequences of brain injury, such as AD-like degeneration, for which neuroprotective therapy is urgently needed.

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The role of heat shock proteins Hsp70 and Hsp27 in cellular protection of the central nervous system

Cited by 192 publications

References 73 publications

Novel Mouse Model of Monocular Amaurosis Fugax

Novel Mouse Model of Monocular Amaurosis Fugax

Different anti-aggregation and pro-degradative functions of the members of the mammalian sHSP family in neurological disorders

Dynamics of endogenous Hsp70 synthesis in the brain of olfactory bulbectomized mice

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