Heat shock response and ionstasis: axis against neurodegeneration

Kourtis, Nikos; Nikoletopoulou, Vassiliki; Tavernarakis, Nektarios

doi:10.18632/aging.100517

Cited by 3 publications

(2 citation statements)

References 9 publications

(9 reference statements)

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“…4,30,31 We can hypothesize that the hereditary impairment of mRNA expression of aB-crystallin (Cryab) gene in OXYS rats 23 and the same deficiency demonstrated here (the reduced level of the aB-crystallin protein in the OXYS retina)-in conjunction with the inability to fully respond to stress-can contribute to the development of AMD-like retinopathy in OXYS rats.…”

Section: Discussionmentioning

confidence: 61%

The mitochondria-targeted antioxidant SkQ1 restoresαB-crystallin expression and protects against AMD-like retinopathy in OXYS rats

et al. 2014

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Abbreviations: AMD, age-related macular degeneration; RPE, retinal pigment epithelium; SkQ1, 10-(6 0 plastoquinonyl)decyltriphenylphosphonium.Age-related macular degeneration (AMD), a neurodegenerative and vascular retinal disease, is the leading cause of blindness in the developed world. Accumulating evidence suggests that alterations in the expression of a small heat shock protein (aB-crystallin) are involved in the pathogeneses of AMD. Here we demonstrate that senescenceaccelerated OXYS rats-an animal model of the dry form of AMD-develop spontaneous retinopathy against the background of reduced expression of aB-crystallin in the retina at the early preclinical stages of retinopathy (age 20 days) as well as at 4 and 24 months of age, during the progressive stage of the disease. The level of aA-crystallin expression in the retina of OXYS rats at all the ages examined was no different from that in disease-free Wistar rats. Treatment with the mitochondria-targeted antioxidant SkQ1 (plastoquinonyl-decyltriphenylphosphonium) from 1.5 to 4 months of age, 250 nmol/kg, increased the level of aB-crystallin expression in the retina of OXYS rats. SkQ1 slowed the development of retinopathy and reduced histological aberrations in retinal pigment epithelium cells. SkQ1 also attenuated neurodegenerative changes in the photoreceptors and facilitated circulation in choroid blood vessels in the retina of OXYS rats; this improvement was probably linked with the restoration of aB-crystallin expression.

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Section: Discussionmentioning

confidence: 61%

The mitochondria-targeted antioxidant SkQ1 restoresαB-crystallin expression and protects against AMD-like retinopathy in OXYS rats

et al. 2014

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“…In addition to calcium, SPCAs transports Magnesium (Mn 2+ ) to the Golgi lumen to regulate both the physiology and pathophysiology of the cells (Brini and Carafoli, 2009;Shull, 2000;Vangheluwe et al, 2009;Vanoevelen et al, 2007). As with the ER, the specific roles of SPCAs in neurons have not been studied extensively, but a study suggests that they (Kourtis et al, 2012).…”

Section: A Reservoir For Ca 2+ Ionsmentioning

confidence: 99%

Pharmacological Regulation of Endoplasmic Reticulum Structure and Calcium Dynamics: Importance for Neurodegenerative Diseases

et al. 2023

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The endoplasmic reticulum (ER) is the largest organelle of the cell, composed of a continuous network of sheets and tubules, and is involved in protein, calcium (Ca 2+ ) and lipid homeostasis. In neurons, the ER extends throughout the cell, both somal and axodendritic compartments, and is highly important for neuronal functions. A third of the proteome of a cell, secreted and membrane-bound proteins, are processed within the ER lumen and most of these proteins are vital for neuronal activity. The brain itself is high in lipid content and many structural lipids are produced, in part, by the ER. Cholesterol and steroid synthesis are strictly regulated in the ER of the blood-brain barrier protected brain cells. The high Ca 2+ level in the ER lumen and low cytosolic concentration is needed for Ca 2+based intracellular signaling, also for synaptic signaling and Ca 2+ waves, as well as preparing proteins for correct folding in the presence of high Ca 2+ concentrations to cope with the high concentrations of extracellular milieu. Particularly, ER Ca 2+ is controlled in axodendritic areas for proper neurito-and synaptogenesis and synaptic plasticity and remodeling. In this review, we cover the physiological functions of the neuronal ER and discuss it in context of common neurodegenerative diseases focusing on pharmacological regulation of ER Ca 2+ . Furthermore, we postulate that heterogeneity of the ER, its protein folding capacity and ensuring Ca 2+ regulation is a crucial factor for the aging and selective vulnerability of neurons in various neurodegenerative diseases.Significance statement ER Ca 2+ regulators are promising therapeutic targets for degenerative diseases for which efficacious drug therapies do not exist. The use of pharmacological probes targeting maintenance and restoration of ER Ca 2+ can provide restoration of protein homeostasis, e.g. folding of complex plasma membrane signalling receptors and slow down the degeneration process of neurons.

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Heat shock response and ionstasis: axis against neurodegeneration

Cited by 3 publications

References 9 publications

The mitochondria-targeted antioxidant SkQ1 restoresαB-crystallin expression and protects against AMD-like retinopathy in OXYS rats

The mitochondria-targeted antioxidant SkQ1 restoresαB-crystallin expression and protects against AMD-like retinopathy in OXYS rats

Pharmacological Regulation of Endoplasmic Reticulum Structure and Calcium Dynamics: Importance for Neurodegenerative Diseases

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