oalib

Publish in OALib Journal

ISSN: 2333-9721

APC: Only $99

Submit

Any time

2019 ( 184 )

2018 ( 278 )

2017 ( 279 )

2016 ( 379 )

Custom range...

Search Results: 1 - 10 of 219518 matches for " Nibaldo C. Inestrosa "
All listed articles are free for downloading (OA Articles)
Page 1 /219518
Display every page Item
EL APORTE DE LUCO A LA NEUROCIENCIA CHILENA
NIBALDO C INESTROSA
Biological Research , 2003,
Abstract:
Abstract
Nibaldo Inestrosa C.
Biological Research , 2000,
Abstract:
Interactions of AChE with Aβ Aggregates in Alzheimer’s Brain: Therapeutic Relevance of IDN 5706
Nibaldo C. Inestrosa
Frontiers in Molecular Neuroscience , 2011, DOI: 10.3389/fnmol.2011.00019
Abstract: Acetylcholinesterase (AChE; EC 3.1.1.7) plays a crucial role in the rapid hydrolysis of the neurotransmitter acetylcholine, in the central and peripheral nervous system and might also participate in non-cholinergic mechanism related to neurodegenerative diseases. Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by a progressive deterioration of cognitive abilities, amyloid-β (Aβ) peptide accumulation and synaptic alterations. We have previously shown that AChE is able to accelerate the Aβ peptide assembly into Alzheimer-type aggregates increasing its neurotoxicity. Furthermore, AChE activity is altered in brain and blood of Alzheimer’s patients. The enzyme associated to amyloid plaques changes its enzymatic and pharmacological properties, as well as, increases its resistant to low pH, inhibitors and excess of substrate. Here, we reviewed the effects of IDN 5706, a hyperforin derivative that has potential preventive effects on the development of AD. Our results show that treatment with IDN 5706 for 10 weeks increases brain AChE activity in 7-month-old double transgenic mice (APPSWE–PS1) and decreases the content of AChE associated with different types of amyloid plaques in this Alzheimer’s model. We concluded that early treatment with IDN 5706 decreases AChE–Aβ interaction and this effect might be of therapeutic interest in the treatment of AD.
The role of Wnt signaling in neuronal dysfunction in Alzheimer's Disease
Nibaldo C Inestrosa, Enrique M Toledo
Molecular Neurodegeneration , 2008, DOI: 10.1186/1750-1326-3-9
Abstract: Alzheimer's disease (AD) is a neurodegenerative disorder associated with aging and characterized by fibrillar deposits of Aβ in subcortical brain regions. Typical features of AD are extracellular neuritic amyloid plaques (senile plaques) and intracellular neurofibrillary tangles. The main proteinaceous component of the amyloid deposited in AD is the Aβ peptide, a 40-to 42-residue peptide that has been isolated from senile plaque cores. Studies in AD mouse models and AD patients support the hypothesis that Aβ causes "synaptic failure" before plaques develop and neuronal cell death occurs; such effects are produced by Aβ oligomers, which are soluble and toxic molecular forms of Aβ [1].The importance of Wnt (wingless-type murine-mammary-tumour virus integration site) signaling in many adult and developmental processes, such as gastrulation, axis formation, cell polarity, organ development and maintenance of stem cell pluripotency, is widely acknowledged [2,3]. In embryos, signaling by Wnt factors controls the organization of the body plan during the early stages of development as well as organogenesis at later developmental stages. Postnatally, Wnt signaling is involved in normal biological events such as tissue maturation and homeostasis and in several neoplastic pathologies. In the mammalian central nervous system (CNS), Wnt signal transduction is involved in neural induction and patterning in early embryogenesis; previous studies have also linked Wnt signaling to neurodegenerative disorders such as AD [4-6]. In fact, strong evidence suggests that a loss of Wnt function is implicated in the pathophysiology of neuronal degeneration of AD. Wnt signaling is complex; 19 mammalian Wnt genes have been cloned, and more than ten membrane receptors and a plethora of cofactors and regulators are known. Different mechanisms of Wnt signaling have also been identified. The best understood of these is the "canonical" pathway, in which β-catenin transduces the Wnt signal to the nuc
Wnt signaling in the regulation of adult hippocampal neurogenesis
Lorena Varela-Nallar,Nibaldo C. Inestrosa
Frontiers in Cellular Neuroscience , 2013, DOI: 10.3389/fncel.2013.00100
Abstract: In the adult brain new neurons are continuously generated mainly in two regions, the subventricular zone (SVZ) of the lateral ventricles and the subgranular zone (SGZ) in the hippocampal dentate gyrus. In the SGZ, radial neural stem cells (NSCs) give rise to granule cells that integrate into the hippocampal circuitry and are relevant for the plasticity of the hippocampus. Loss of neurogenesis impairs learning and memory, suggesting that this process is important for adult hippocampal function. Adult neurogenesis is tightly regulated by multiple signaling pathways, including the canonical Wnt/β-catenin pathway. This pathway plays important roles during the development of neuronal circuits and in the adult brain it modulates synaptic transmission and plasticity. Here, we review current knowledge on the regulation of adult hippocampal neurogenesis by the Wnt/β-catenin signaling cascade and the potential mechanisms involved in this regulation. Also we discuss the evidence supporting that the canonical Wnt pathway is part of the signaling mechanisms involved in the regulation of neurogenesis in different physiological conditions. Finally, some unsolved questions regarding the Wnt-mediated regulation of neurogenesis are discussed.
Postsynaptic Receptors for Amyloid-β Oligomers as Mediators of Neuronal Damage in Alzheimer’s Disease
Juvenal A. Ríos,Nibaldo C. Inestrosa
Frontiers in Physiology , 2012, DOI: 10.3389/fphys.2012.00464
Abstract: The neurotoxic effect of amyloid-β peptide (Aβ) over the central synapses has been described and is reflected in the decrease of some postsynaptic excitatory proteins, the alteration in the number and morphology of the dendritic spines, and a decrease in long-term potentiation. Many studies has been carried out to identify the putative Aβ receptors in neurons, and is still no clear why the Aβ oligomers only affect the excitatory synapses. Aβ oligomers bind to neurite and preferentially to the postsynaptic region, where the postsynaptic protein-95 (PSD-95) is present in the glutamatergic synapse, and interacts directly with the N-methyl-D-aspartate receptor (NMDAR) and neuroligin (NL). NL is a postsynaptic protein which binds to the presynaptic protein, neurexin to form a heterophilic adhesion complex, the disruption of this interaction affects the integrity of the synaptic contact. Structurally, NL has an extracellular domain homolog to acetylcholinesterase, the first synaptic protein that was found to interact with Aβ. In the present review we will document the interaction between Aβ and the extracellular domain of NL-1 at the excitatory synapse, as well as the interaction with other postsynaptic components, including the glutamatergic receptors (NMDA and mGluR5), the prion protein, the neurotrophin receptor, and the α7-nicotinic acetylcholine receptor. We conclude that several Aβ oligomers receptors exist at the excitatory synapse, which could be the responsible for the neurotoxic effect described for the Aβ oligomers. The characterization of the interaction between Aβ receptors and Aβ oligomers could help to understand the source of the neurologic damage observed in the brain of the Alzheimer’s disease patients.
Amyloid-?-peptide reduces copper(II) to copper(I) independent of its aggregation state
OPAZO,CARLOS; RUIZ,FRANCISCA H; INESTROSA,NIBALDO C;
Biological Research , 2000, DOI: 10.4067/S0716-97602000000200012
Abstract: alzheimer?s disease (ad) is characterized by the deposition of amyloid b-peptide (a?) and neuronal degeneration in brain regions involved in learning and memory. one of the leading etiologic hypotheses regarding ad is the involvement of free radical-mediated oxidative stress in neuronal degeneration. recent evidence suggests that metals concentrated in amyloid deposits may contribute to the oxidative insults observed in ad-affected brains. we hypothesized that a? peptide in the presence of copper enhances its neurotoxicity generating free radicals via copper reduction. in the present study, we have examined the effect of the aggregation state of amyloid-?-peptide on copper reduction. in independent experiments we measured the copper-reducing ability of soluble and fibrillar a?1-40 forms by bathocuproine assays. as it was previously observed for the amyloid precursor protein (app), the a? peptide showed copper-reducing ability. the capacity of a? to reduce copper was independent of the aggregation state. finally, the a? peptide derived from the human sequence has a greater effect than the a? peptide derived from the rat sequence, suggesting that histidine 13 may play a role in copper reduction. in agreement with this possibility, the a? peptide reduces less copper in the presence of exogenous histidine
Contributions by researchers of "Ciencia de Frontera" of the Chilean Academy of Sciences
CHRISTIAN GONZALEZ-BILLAUL,NIBALDO C INESTROSA,MANUEL J SANTOS
Biological Research , 2011,
Abstract:
Amyloid- -peptide reduces copper(II) to copper(I) independent of its aggregation state
CARLOS OPAZO,FRANCISCA H RUIZ,NIBALDO C INESTROSA
Biological Research , 2000,
Abstract: Alzheimer’s disease (AD) is characterized by the deposition of amyloid b-peptide (A ) and neuronal degeneration in brain regions involved in learning and memory. One of the leading etiologic hypotheses regarding AD is the involvement of free radical-mediated oxidative stress in neuronal degeneration. Recent evidence suggests that metals concentrated in amyloid deposits may contribute to the oxidative insults observed in AD-affected brains. We hypothesized that A peptide in the presence of copper enhances its neurotoxicity generating free radicals via copper reduction. In the present study, we have examined the effect of the aggregation state of amyloid- -peptide on copper reduction. In independent experiments we measured the copper-reducing ability of soluble and fibrillar A 1-40 forms by bathocuproine assays. As it was previously observed for the amyloid precursor protein (APP), the A peptide showed copper-reducing ability. The capacity of A to reduce copper was independent of the aggregation state. Finally, the A peptide derived from the human sequence has a greater effect than the A peptide derived from the rat sequence, suggesting that histidine 13 may play a role in copper reduction. In agreement with this possibility, the A peptide reduces less copper in the presence of exogenous histidine
Axotomy-induced neurotrophic withdrawal causes the loss of phenotypic differentiation and downregulation of NGF signalling, but not death of septal cholinergic neurons
Oscar M Lazo, Jocelyn C Mauna, Claudia A Pissani, Nibaldo C Inestrosa, Francisca C Bronfman
Molecular Neurodegeneration , 2010, DOI: 10.1186/1750-1326-5-5
Abstract: The principal aim of this study was to evaluate, using modern quantitative confocal microscopy, neurodegenerative changes in septal cholinergic neurons after axotomy and to assess their response to delayed infusion of NGF in rats.We found that there is a slow reduction of cholinergic cells labeled by ChAT and p75 after axotomy. However, this phenomenon is not accompanied by neurodegenerative changes or by a decrease in total neuronal number in the medial septum. Although the remaining axotomized-neurons appear healthy, they are unable to respond to delayed NGF infusion.Our results demonstrate that at 3 weeks, axotomized cholinergic neurons lose their cholinergic phenotype without dying and down-regulate their NGF-receptors, precluding the possibility of a response to NGF. Therefore, the physiological role of NGF in the adult septal cholinergic system is to support phenotypic differentiation and not survival of neurons. This evidence raises questions about the relationship between transcriptional regulation of the cholinergic phenotype by retrograde-derived trophic signaling and the transcriptional changes experienced when retrograde transport is impaired due to neuropathological conditions.Basal forebrain cholinergic neurons (BFCN) account for most of the cholinergic innervation of the hippocampus and cortical mantle, and have a key role in the regulation of synaptic activity and modulation of memory and attention in rodents, primates and humans [1-5].The physiology of septal cholinergic neurons is regulated by the trophic support offered by their target, the hippocampus. Disconnection of septal cholinergic neurons from their target by an experimental transection of the fimbria-fornix, reduces the number of neurons positive for cholinergic markers such as choline acetyl transferase (ChAT) [1,6-13]. One of the best-studied trophic factors for septal cholinergic neurons is nerve growth factor (NGF). Levels of NGF mRNA and protein are consistently detected in the hippo
Page 1 /219518
Display every page Item


Home
Copyright © 2008-2017 Open Access Library. All rights reserved.