Abnormal calcium homeostasis in peripheral neuropathies

Fernyhough, Paul; Calcutt, Nigel A.

doi:10.1016/j.ceca.2009.11.008

Cited by 112 publications

(74 citation statements)

References 152 publications

(165 reference statements)

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“…Thus, abnormal Ca 2ϩ homeostasis has been implicated in the induction of axonal degeneration in peripheral neuropathies (49). Furthermore, increases in intracellular Ca 2ϩ regulate protein kinases, such as, Rho-associated kinase, myosin light chain kinase, and LIM kinases, which modify actin dynamics (50 -52).…”

Section: Discussionmentioning

confidence: 99%

Axonal Neuropathy-associated TRPV4 Regulates Neurotrophic Factor-derived Axonal Growth

Jang

Jung

Kim

et al. 2012

Journal of Biological Chemistry

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Background:Because genetic linkage studies identified mutations in TRPV4 in patients with peripheral neuropathies, the function of TRPV4 in peripheral neurons is questioned. Results: TRPV4 was found to promote neurotrophic factor-driven neuritogenesis. Conclusion: TRPV4 mediates neurotrophic factor-driven neuritogenesis in peripheral neurons. Significance: This explains molecular mechanisms underlying neuritogenesis and maintenance of peripheral nerves.

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Section: Discussionmentioning

confidence: 99%

Axonal Neuropathy-associated TRPV4 Regulates Neurotrophic Factor-derived Axonal Growth

Jang

Jung

Kim

et al. 2012

Journal of Biological Chemistry

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“…Impaired mitochondrial function and oxidative stress in Schwann cells (see above) could lead to changes in the distribution of Na V and K V channels at the nodes of Ranvier and the paranodal and juxataparanodal regions, contributing to axonal damage. Mitochondrial dysfunction may also be a consequence of increased intracellular calcium 135 . A detailed discussion of the role of ion channels in diabetic neuropathy is beyond the scope of this Review, but abnormalities such as paranodal swelling and axon-glial disjunction have been described in diabetic neuropathy in humans, and were proposed as a cause of nodal ion channel redistribution 136 .…”

Section: Microvascular Changes and Schwann Cells Microvascular Damagmentioning

confidence: 99%

Schwann cell interactions with axons and microvessels in diabetic neuropathy

et al. 2017

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The incidence of diabetes mellitus has increased dramatically over the past two to three decades. According to the International Diabetes Federation Diabetes Atlas, 415 million people worldwide had diabetes in 2015, and this number is expected to grow by 5% annually, predominantly as a result of increasing prevalence of type 2 diabetes. Furthermore, an estimated 100 million Europeans and 80 million Americans have impaired glucose tolerance or prediabetes. Few people die from acute diabetes in countries with comprehensive health care systems, but the disease is inflicting a huge medical, social and economic burden on society owing to the need for lifelong treatment of its systemic consequences and the insidious development of multi-organ damage.Peripheral neuropathy (BOXES 1,2) is a common but often neglected complication of long-term diabetes, and the lack of treatment options reflects an incomplete understanding of the pathogenic mechanisms. Hyperglycaemia is generally accepted as the primary pathogenic insult in type 1 and type 2 diabetic neuropathy, although roles are emerging for other factors, such as impaired insulin signalling, hypertension and dyslipidaemia (particularly for type 2 diabetes), which might precede overt hyperglycaemia 1 . Many preclinical studies, and occasional clinical studies, have indicated that diabetic neuropathy -like diabetic nephropathy and retinopathy -results from microvascular disease, with a focus on axonal degeneration as a consequence of ischaemia and/or hypoxia. This mechanism, however, is likely to be only one aspect of a more complex pathogenesis.The earliest descriptions of pathology in diabetic neuropathy indicated that Schwannopathy accompanied axonal degeneration. The majority of clinical and basic research in diabetic neuropathy since then has focused on the effects on neurons. However, accumulating data from research into the development and regeneration of the PNS has identified Schwann cells as equally indispensable components that maintain neuronal structure and function, nourish axons, and promote survival and growth upon injury. The early reports from 1979 that demonstrated morphological changes in Schwann cells in human diabetic neuropathy 2 are now supported by an increased awareness of molecular alterations in Schwann cells during diabetes 3 . Schwann cells express a wide range of receptors and, when they sense insults or danger signals, they upregulate synthesis and secretion of factors that stimulate neuroprotection, regrowth and remyelination, or factors that aggravate disease phenotypes 4 . The most recent studies have demonstrated that Schwann cells regulate many aspects of axonal function, so that disruption of their metabolism by diabetes results in the accumulation of neurotoxic intermediates and compromises production of neuronal support factors, contributing to axonal degeneration, endothelial dysfunction and diabetic neuropathy. Abstract | The prevalence of diabetes worldwide is at pandemic levels, with the number of patients increasing by 5% annu...

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“…Evidence for the involvement of perturbed Ca 2ϩ regulation in peripheral nerve cells in PN has been reviewed (Fernyhough and Calcutt, 2010). ER Ca 2ϩ signaling is altered in sensory neurons in animal models of PN.…”

Section: Peripheral Neuropathies and Amyotrophic Lateral Sclerosismentioning

confidence: 99%