Calcium ions in neuronal degeneration

Wojda, Urszula; Salińska, Elżbieta; Kuźnicki, Jacek

doi:10.1002/iub.91

Cited by 268 publications

(214 citation statements)

References 181 publications

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“…C ells must tightly regulate Ca 2+ homeostasis to avoid pathological perturbations and cell death (1). For example, a profound disruption of Ca 2+ homeostasis is seen in Parkinson disease (PD), the second most common neurodegenerative disorder.…”

mentioning

confidence: 99%

Calcineurin determines toxic versus beneficial responses to α-synuclein

Caraveo

Auluck

Whitesell

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

105

144

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Calcineurin (CN) is a highly conserved Ca 2+ -calmodulin (CaM)-dependent phosphatase that senses Ca 2+ concentrations and transduces that information into cellular responses. Ca 2+ homeostasis is disrupted by α-synuclein (α-syn), a small lipid binding protein whose misfolding and accumulation is a pathological hallmark of several neurodegenerative diseases. We report that α-syn, from yeast to neurons, leads to sustained highly elevated levels of cytoplasmic Ca 2+ , thereby activating a CaM-CN cascade that engages substrates that result in toxicity. Surprisingly, complete inhibition of CN also results in toxicity. Limiting the availability of CaM shifts CN's spectrum of substrates toward protective pathways. Modulating CN or CN's substrates with highly selective genetic and pharmacological tools (FK506) does the same. FK506 crosses the blood brain barrier, is well tolerated in humans, and is active in neurons and glia. Thus, a tunable response to CN, which has been conserved for a billion years, can be targeted to rebalance the phosphatase's activities from toxic toward beneficial substrates. These findings have immediate therapeutic implications for synucleinopathies.

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mentioning

confidence: 99%

Calcineurin determines toxic versus beneficial responses to α-synuclein

Caraveo

Auluck

Whitesell

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

105

144

View full text Add to dashboard Cite

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“…It has been showed that ROS mediated dysregulation of intracellular calcium signaling pathways affected the cell severely. Altered calcium homeostasis could further initiate the excitotoxic effects which lead to activation of glutamate receptors and neuronal apoptosis under diseased condition [59][60][61][62] .…”

Section: (B)mentioning

confidence: 99%

Antioxidants as a preventive therapeutic option for age related neurodegenerative diseases

Singh

2015

Ther Targets Neurol Dis

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Neurodegenerative diseases: an overview -Neurodegenerative disease term illustrate a range of conditions in which primarily neurons get affected or die. Neurons are the building blocks of the central and peripheral nervous system. Neurons could not reproduce or replace themselves with age therefore, when they get damaged or die they cannot be replaced and lead to specific neurodegenerative disease. Few evidences for the presence of stem cells are reported [1] but still it is not understood whether damaged neuron could regenerate or not. The Parkinson's, Alzheimer's, and Huntington's diseases are the most prevalent age related neurodegenerative diseases of central nervous system involving death of specific neuronal population. The treatment of these neurodegenerative diseases might involve the re-supplementation of specific neuronal population with the help of stem cells but researchers and clinicians did not get noticeable success in this approach yet. Millions of people each year are getting affected by these neurodegenerative diseases and the incidences are increasing further significantly with the extended life expectancy. It has been reported by World Health Organisation (2006) that the number of older people of more than 65 years age are expected to increase to approximately 1 billion in 2030 worldwide. Developing countries like India and China will see the largest increase in numbers of aged persons. Therefore the percentage of aged population in developing countries would increase from 59% to 71% worldwide [2] . Since occurrence of most of the neurodegenerative Advances in our understanding for neurodegenerative mechanisms have increased significantly in last few decades. But still no novel disease modifying therapy has been developed which could prevent the disease progression and drawn our attention towards the development of new alternative therapy. The major obstacle for the development of disease therapy is incomplete knowledge about neurodegenerative mechanisms. Due to the insufficient information about neurodegenerative mechanisms no standard diagnostic tests for the detection of neurodegenerative disease could be develop to date, causes delayed diagnosis and disease worsening. So far the exploratory reports and clinical data have suggested the involvement of oxidative stress, mitochondrial impairment and apoptosis as major neurodegenerative mechanisms. Investigations have elicited that once initiated the degeneration of neurons could not be arrested therefore in the scarcity of curative therapy we should approach for the preventive neurodegenerative therapy. Since oxidative stress has noteworthy involvement in neuronal death solely, and in connection to other death pathways therefore, antioxidants as preventive therapeutics might provide beneficial effects in age related neurodegenerative diseases. With this hypothesis in this review we are discussing about the use of antioxidants as a preventive treatment of neurodegenerative diseases. Such therapies may work in the preventive phase or in curati...

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“…NMDA receptors permit calcium to enter the cell when combining with glutamate, which is imperative for cell signaling, and then for learning and memory [112]. However, excess glutamate can be released from impaired neurons in AD, resulting in chronic overexposure to calcium, which can in turn accelerate neuron impairment [113]. Memantine can partially block the NMDA receptors, and then prevent this destructive chain of events [108,109].…”

Section: Symptomatic Therapies: Approved Drugs For Treatment In Alzhementioning

confidence: 99%