NGF mRNA is not decreased in frontal cortex from Alzheimer's Disease patients

Jetté, Nathalie; Cole, M.S.; Fahnestock, Margaret

doi:10.1016/0169-328x(94)90159-7

Cited by 66 publications

(31 citation statements)

References 48 publications

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“…Age-related reductions in NGF production in the cortex have not been reported either in the context of normal or pathological aging (52)(53)(54)(55). On the other hand, reductions in expression of neurotrophin receptors in basal forebrain cholinergic neurons have been reported in Alzheimer's disease (56,57) but not in normal aging.…”

Section: Discussionmentioning

confidence: 87%

Nontropic actions of neurotrophins: Subcortical nerve growth factor gene delivery reverses age-related degeneration of primate cortical cholinergic innervation

Conner

Darracq

Roberts³

et al. 2001

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

106

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Normal aging is associated with a significant reduction in cognitive function across primate species. However, the structural and molecular basis for this age-related decline in neural function has yet to be defined clearly. Extensive cell loss does not occur as a consequence of normal aging in human and nonhuman primate species. More recent studies have demonstrated significant reductions in functional neuronal markers in subcortical brain regions in primates as a consequence of aging, including dopaminergic and cholinergic systems, although corresponding losses in cortical innervation from these neurons have not been investigated. In the present study, we report that aging is associated with a significant 25% reduction in cortical innervation by cholinergic systems in rhesus monkeys (P < 0.001). Further, these age-related reductions are ameliorated by cellular delivery of human nerve growth factor to cholinergic somata in the basal forebrain, restoring levels of cholinergic innervation in the cortex to those of young monkeys (P ‫؍‬ 0.89). Thus, (i) aging is associated with a significant reduction in cortical cholinergic innervation; (ii) this reduction is reversible by growth-factor delivery; and (iii) growth factors can remodel axonal terminal fields at a distance, representing a nontropic action of growth factors in modulating adult neuronal structure and function (i.e., administration of growth factors to cholinergic somata significantly increases axon density in terminal fields). These findings are relevant to potential clinical uses of growth factors to treat neurological disorders.aging ͉ Alzheimer's disease ͉ gene therapy ͉ plasticity ͉ cholinergic systems

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Section: Discussionmentioning

confidence: 87%

Nontropic actions of neurotrophins: Subcortical nerve growth factor gene delivery reverses age-related degeneration of primate cortical cholinergic innervation

Conner

Darracq

Roberts³

et al. 2001

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

106

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“…Since NGF mRNA is unchanged (Goedert et al, 1986;Jetté et al, 1994;Fahnestock et al, 1996), the impairment of NGF axonal transport in AD brain may result in its accumulation at productions sites (hippocampus and neocortical cortex) (Cooper et al, 1994) and in a deficiency at the transport end sites (basal forebrain cholinergic neurons, BFCNs). According to this hypothesis the impairment of NGF transport and the degeneration of cholinergic neurons may be considered one of the earliest events in AD .…”

Section: Ngf and Its Receptors In Admentioning

confidence: 99%

Nerve growth factor as a paradigm of neurotrophins related to Alzheimer's disease

Calissano

Matrone

Amadoro

2010

Developmental Neurobiology

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Converging lines of evidence on the possible connection between NGF signaling and Alzheimer's diseases (AD) are unraveling new facets which could depict this neurotrophin (NTF) in a more central role. AD animal models have provided evidence that a shortage of NGF supply may induce an AD-like syndrome. In vitro experiments, moreover, are delineating a possible temporal and causal link between APP amiloydogenic processing and altered post-translational tau modifications. After NGF signaling interruption, the pivotal upstream players of the amyloid cascade (APP, b-secretase, and active form of c-secretase) are up-regulated, leading to an increased production of amyloid b peptide (Ab) and to its intracellular aggregation in molecular species of different sizes. Contextually, the Ab released pool generates an autocrine toxic loop in the same healthy neurons. At the same time tau protein undergoes anomalous, GSKb-mediated, phosphorylation at specific pathogenetic sites (Ser262 and Thr 231), caspase(s) and calpain-I-mediated truncation, detachment from microtubules with consequent cytoskeleton collapse and axonal transport impairment. All these events are inhibited when the amyloidogenic processing is reduced by b and c secretase inhibitors or anti-Ab antibodies and appear to be causally correlated to TrkA, p75CTF, Ab, and PS1 molecular association in an Ab-mediated fashion. In this scenario, the so-called trophic action exerted by NGF (and possibly also by other neurotrophins) in these targets neurons is actually the result of an anti-amyloidogenic activity. '

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“…This issue was investigated early by many authors who found no evidence for such a deficiency. In most cases, the AD brain revealed normal or augmented NGF mRNA [8,9] and normal or augmented NGF [10][11][12]. More recently, the work of Fahnestock and collaborators [13] clearly indicates that in AD there is an unequivocal up-regulation of the NGF precursor molecule, proNGF.…”

Section: Introductionmentioning

confidence: 98%

The Failure in NGF Maturation and its Increased Degradation as the Probable Cause for the Vulnerability of Cholinergic Neurons in Alzheimer’s Disease

Cuello

Bruno

2007

Neurochem Res

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This short review discusses the arguments to consider the dismetabolism of the pathway responsible for both the maturation and degradation of NGF as the culprit of vulnerability of the forebrain cholinergic system to the Alzheimer's disease neuropathology. This summary includes information regarding a novel metabolic cascade converting Pro-NGF to mature NGF in the extracellular space and its ultimate degradation by a metalloprotease. It also describes how this pathway is altered in Alzheimer's disease with the consequential CNS accumulation of proNGF and impairment in the formation of NGF along with increased degradation of this key trophic factor. This metabolic scenario in Alzheimer's disease should result in the failure of NGF trophic support to forebrain cholinergic neurons and thus explaining the vulnerability of these neurons in this neurodegenerative condition.

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NGF mRNA is not decreased in frontal cortex from Alzheimer's Disease patients

Cited by 66 publications

References 48 publications

Nontropic actions of neurotrophins: Subcortical nerve growth factor gene delivery reverses age-related degeneration of primate cortical cholinergic innervation

Nontropic actions of neurotrophins: Subcortical nerve growth factor gene delivery reverses age-related degeneration of primate cortical cholinergic innervation

Nerve growth factor as a paradigm of neurotrophins related to Alzheimer's disease

The Failure in NGF Maturation and its Increased Degradation as the Probable Cause for the Vulnerability of Cholinergic Neurons in Alzheimer’s Disease

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