Regional changes of ciliary neurotrophic factor and nerve growth factor levels in post mortem spinal cord and cerebral cortex from patients with motor disease

Anand, Praveen; Parrett, Alison; Martin, Joanne E.; Zeman, Sophie; Foley, Peter J.; Swash, Michael; Leigh, P. Nigel; Cedarbaum, Jesse M.; Lindsay, Ronald M.; Williams-Chestnut, R.E.

doi:10.1038/nm0295-168

Cited by 66 publications

(37 citation statements)

References 31 publications

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“…CNTF decreased in the spinal cord from ALS patients as compared with control subjects, in both homozygotes and heterozygotes, suggesting that a decrease in CNTF levels in the spinal cord is a feature of ALS. Our results are consistent with the report of Anand et al [23], although we expressed concentration of CNTF as nanograms per gram of soluble protein and they expressed it as nanograms per gram of wet tissue.…”

Section: Discussionsupporting

confidence: 92%

“…Schorr et al [22]analyzed postmortem paraffin sections of the spinal cord of 7 ALS patients, and found CNTF immunoreactivity in most of the motor neurons of the ventral horn in 5 cases, while in 2 cases, the number of positively stained motor neurons was less. Anand et al [23]reported a marked decrease in CNTF in the spinal cord in ALS using an EIA method. They also reported that in the spinal cord from ALS patients, there was a marked increase in the hybridization signal for mRNA of the alpha subunit of the CNTF receptor [24].…”

Section: Discussionmentioning

confidence: 99%

“…Degeneration of the anterior horn and the lateral corticospinal tract was confirmed histologically in all the ALS spinal cords. CNTF may be present in glial cells and/or motor neurons [23]. Thus, it is likely that the decreased CNTF levels in the lateral corticospinal tract in the spinal cord from ALS patients reflect altered expression by glial cells, some of which surround the motor neuron, or may simply relate to oligodendrocyte loss secondary to axonal degeneration.…”

Section: Discussionmentioning

confidence: 99%

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Decrease in the Ciliary Neurotrophic Factor of the Spinal Cord in Amyotrophic Lateral Sclerosis

Ono

Imai

Igarashi³

et al. 1999

Eur Neurol

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Ciliary neurotrophic factor (CNTF), a potent survival factor in spinal motoneurons of embryonic chick and rat, is currently being investigated in humans as a treatment for amyotrophic lateral sclerosis (ALS). However, its physiological and pathological activities in ALS remain unclear. We measured CNTF contents in the cervical enlargement of the spinal cord from 9 ALS patients and 12 age-matched control subjects using a sensitive enzyme-linked immunoassay. CNTF genotypes were determined by the polymerase chain reaction-restriction fragment length polymorphism method. In control subjects, there were 8 homozygotes and 4 heterozygotes, while in ALS patients there were 6 and 3, respectively. In both homozygotes and heterozygotes, CNTF expression in the spinal cord from ALS patients tended to decrease compared to control subjects. In homozygotes, the decrease was significant (p < 0.05). Concerning the regional concentrations of CNTF, in homozygotes, CNTF contents in the lateral corticospinal tract were markedly lower (p < 0.001) in ALS patients than in controls. The decrease in CNTF expression in the lateral corticospinal tract of the spinal cord from ALS patients may be a feature of ALS and could be related to motor neuron loss.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Decrease in the Ciliary Neurotrophic Factor of the Spinal Cord in Amyotrophic Lateral Sclerosis

Ono

Imai

Igarashi³

et al. 1999

Eur Neurol

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“…In spinal cord motor neuron areas from ALS patients, no specific expression of NGF or its corresponding high affinity receptor trk A have been detected [51]. Motor cortex from patients suffering from ALS have revealed decreased levels of NGF compared to control brains [71]. In a recent study, increased levels of NGF in postmortem muscle tissue from patients with ALS was observed [16].…”

Section: Neurotrophinsmentioning

confidence: 98%

Neurotrophic Factors and Amyotrophic Lateral Sclerosis

Ekestern

2004

Neurodegener Dis

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The cause of motor neuron death in amyotrophic lateral sclerosis (ALS) remains a mystery. Initial implications of neurotrophic factor impairment involved in disease progression causing selective motor neuron death were brought forward in the late 1980s. These implications were based on several in vitro studies of motor neuron cultures in which a near to complete rescue of axotomized neonatal motor neurons in the presence of supplementary neurotrophic factors were revealed. These findings pawed the way for extensive investigations in experimental animal models of ALS. Neurotrophic factor administration in rodent ALS models demonstrated a remarkable effect on survival of degenerating motor neurons and rescue of axotomized motor neurons, both in vivo and in vitro. In the absence of efficient therapy for ALS, some of these promising neurotrophic factors have been administered to groups of ALS patients, as they appeared available for clinical trials. Up to date, none of tested factors has lived up to expectations, altering the outcome of the disease. This review summarizes current findings on neurotrophic factor expression in ALS tissue and these factors’ potential/debatable clinical relevance to ALS and the treatment of ALS. It also discusses possible interventions improving clinical trial design to obtain efficacy of neurotrophic factor treatment in patients suffering from ALS.

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“…However, recent studies strongly suggest that the absence of CNTF modifies the course of some important neurological diseases. Postmortem spinal cord samples from patients with amyotrophic lateral sclerosis (ALS) showed decreased levels of CNTF (38), and in patients with ALS due to a mutation of the superoxide dismutase gene, CNTF deficiency was associated with an earlier onset and a more severe course of the disease (39). CNTF-deficient patients also displayed a significantly earlier onset of multiple sclerosis (MS) and more severe symptoms (40).…”

mentioning

confidence: 99%

Signaling of Human Ciliary Neurotrophic Factor (CNTF) Revisited

Schuster

Kovaleva

Sun³

et al. 2003

Journal of Biological Chemistry

127

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Human ciliary neurotrophic factor (CNTF) is a neurotrophic cytokine that exerts a neuroprotective effect in multiple sclerosis and amyotrophic lateral sclerosis. Clinical application of human CNTF, however, was prevented by high toxicity at higher dosages. Human CNTF elicits cellular responses by induction of a receptor complex consisting of the CNTF ␣-receptor (CNTFR), which is not involved in signal transduction, and the ␤-receptors gp130 and leukemia inhibitory factor receptor (LIFR). Previous studies with rat CNTF demonstrated that rat CNTF is unable to interact with the human interleukin-6 ␣-receptor, whereas at high concentrations, it can directly induce a signaling heterodimer of human gp130 and human LIFR in the absence of the CNTF receptor. Here, we demonstrate that human CNTF cannot directly induce a heterodimer of human gp130 and LIFR. However, human CNTF can use both the membrane-bound and the soluble human IL-6R as a substitute for its cognate ␣-receptor and thus widen the target spectrum of human CNTF. Engineering a CNTFRspecific human CNTF variant may therefore be a prerequisite to improving the safety profile of CNTF.

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Regional changes of ciliary neurotrophic factor and nerve growth factor levels in post mortem spinal cord and cerebral cortex from patients with motor disease

Cited by 66 publications

References 31 publications

Decrease in the Ciliary Neurotrophic Factor of the Spinal Cord in Amyotrophic Lateral Sclerosis

Decrease in the Ciliary Neurotrophic Factor of the Spinal Cord in Amyotrophic Lateral Sclerosis

Neurotrophic Factors and Amyotrophic Lateral Sclerosis

Signaling of Human Ciliary Neurotrophic Factor (CNTF) Revisited

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