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1.
Front Oncol ; 11: 783744, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35004304

RESUMO

BACKGROUND: Aspartate ß-hydroxylase (ASPH) is an embryonic transmembrane protein aberrantly upregulated in cancer cells, associated with malignant transformation and, in some reports, with poor clinical prognosis. OBJECTIVE: To report the expression patterns of ASPH in acute myeloid leukemia (AML). METHODS: Cell surface expression of ASPH was measured via 8-color multiparameter flow cytometry in 41 AML patient samples (31 bone marrow, 10 blood) using fluorescein isothiocyanate (FITC)-conjugated anti-ASPH antibody, SNS-622. A mean fluorescent intensity (MFI) of 10 was used as a cutoff for ASPH surface expression positivity. Data regarding patient and disease characteristics were collected. RESULTS: ASPH surface expression was found on AML blasts in 16 samples (39%). Higher ASPH expression was seen in myeloblasts of African American patients (p=0.02), but no correlation was found between ASPH expression and other patient or disease characteristics. No association was found between ASPH status and CR rate (p=0.53), EFS (p=0.87), or OS (p=0.17). CONCLUSIONS: ASPH is expressed on blasts in approximately 40% of AML cases, and may serve as a new therapeutically targetable leukemia-associated antigen.

2.
PLoS One ; 13(1): e0191866, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29370277

RESUMO

Chemotherapy-induced cognitive impairment (CICI) occurs in a substantial proportion of treated cancer patients, with no drug currently available for its therapy. This study investigated whether PAN-811, a ribonucleotide reductase inhibitor, can reduce cognitive impairment and related suppression of neurogenesis following chemotherapy in an animal model. Young adult rats in Chemo and Chemo+PAN-811 groups received 3 intraperitoneal (i.p.) injections of methotrexate (MTX) and 5-fluorouracil (5-FU), and those in Saline and Saline+PAN-811 groups received equal volumes of physiological saline at 10-day intervals. PAN-811 in saline was delivered through i.p. injection, 10 min following each saline (Saline+PAN-811 group) or MTX/5-FU (Chemo+PAN-811 group) treatment, while equal volumes of saline were delivered to Saline and Chemo groups. Over Days 31-66, rats were administered tests of spatial memory, nonmatching-to-sample rule learning, and discrimination learning, which are sensitive to dysfunction in hippocampus, frontal lobe and striatum, respectively. On Day 97, neurogenesis was immnunohistochemically evaluated by counting doublecortin-positive (DCX+) cells in the dentate gyrus (DG). The results demonstrated that the Chemo group was impaired on the three cognitive tasks, but co-administration of PAN-811 significantly reduced all MTX/5-FU-induced cognitive impairments. In addition, MTX/5-FU reduced DCX+ cells to 67% of that in Saline control rats, an effect that was completely blocked by PAN-811 co-administration. Overall, we present the first evidence that PAN-811 protects cognitive functions and preserves neurogenesis from deleterious effects of MTX/5-FU. The current findings provide a basis for rapid clinical translation to determine the effect of PAN-811 on CICI in human.


Assuntos
Disfunção Cognitiva/prevenção & controle , Neurogênese/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Piridinas/farmacologia , Tiossemicarbazonas/farmacologia , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Disfunção Cognitiva/induzido quimicamente , Giro Denteado/efeitos dos fármacos , Aprendizagem por Discriminação/efeitos dos fármacos , Modelos Animais de Doenças , Proteína Duplacortina , Inibidores Enzimáticos/farmacologia , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Hipocampo/efeitos dos fármacos , Hipocampo/patologia , Hipocampo/fisiopatologia , Humanos , Aprendizagem/efeitos dos fármacos , Metotrexato/administração & dosagem , Metotrexato/efeitos adversos , Ratos , Ratos Long-Evans , Ribonucleotídeo Redutases/antagonistas & inibidores , Memória Espacial/efeitos dos fármacos
3.
Cancer Biother Radiopharm ; 32(2): 57-65, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28301261

RESUMO

There is a need for novel effective and safe therapies for metastatic breast cancer based on targeting tumor-specific molecular markers of cancer. Human aspartyl (asparaginyl) ß-hydroxylase (HAAH) is a highly conserved enzyme that hydroxylates epidermal growth factor-like domains in transformation-associated proteins and is overexpressed in a variety of cancers, including breast cancer. A fully human monoclonal antibody (mAb) PAN-622 has been developed to HAAH. In this study, they describe the development of PAN-622 mAb as an agent for imaging and radioimmunotherapy of metastatic breast cancer. PAN-622 was conjugated to several ligands such as DOTA, CHXA″, and DTPA to enable subsequent radiolabeling and its immunoreactivity was evaluated by an HAAH-specific enzyme-linked immunosorbent assay and binding to the HAAH-positive cells. As a result, DTPA-PAN-622 was chosen to investigate biodistribution in healthy CD-1 female mice and 4T1 mammary tumor-bearing BALB/c mice. The 111In-DTPA-pan622 mAb concentrated in the primary tumors and to some degree in lung metastases as shown by SPECT/CT and Cherenkov imaging. A pilot therapy study with 213Bi-DTPA-PAN-622 demonstrated a significant effect on the primary tumor. The authors concluded that human mAb PAN-622 to HAAH is a promising reagent for development of imaging and possible therapeutic agents for the treatment of metastatic breast cancer.


Assuntos
Anticorpos Monoclonais/química , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/tratamento farmacológico , Oxigenases de Função Mista/química , Animais , Neoplasias da Mama/radioterapia , Linhagem Celular Tumoral , Diagnóstico por Imagem/métodos , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Ligantes , Camundongos , Camundongos Endogâmicos BALB C , Metástase Neoplásica , Radioimunoterapia/métodos , Distribuição Tecidual
4.
Oxid Med Cell Longev ; 2016: 9392404, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26640619

RESUMO

Chemotherapy often results in cognitive impairment, and no neuroprotective drug is now available. This study aimed to understand underlying neurotoxicological mechanisms of anticancer drugs and to evaluate neuroprotective effects of PAN-811. Primary neurons in different concentrations of antioxidants (AOs) were insulted for 3 days with methotrexate (MTX), 5-fluorouracil (5-FU), or cisplatin (CDDP) in the absence or presence of PAN-811·Cl·H2O. The effect of PAN-811 on the anticancer activity of tested drugs was also examined using mouse and human cancer cells (BNLT3 and H460) to assess any negative interference. Cell membrane integrity, survival, and death and intramitochondrial reactive oxygen species (ROS) were measured. All tested anticancer drugs elicited neurotoxicity only under low levels of AO and elicited a ROS increase. These results suggested that ROS mediates neurotoxicity of tested anticancer drugs. PAN-811 dose-dependently suppressed increased ROS and blocked the neurotoxicity when neurons were insulted with a tested anticancer drug. PAN-811 did not interfere with anticancer activity of anticancer drugs against BNLT3 cells. PAN-811 did not inhibit MTX-induced death of H460 cells but, interestingly, demonstrated a synergistic effect with 5-FU or CDDP in reducing cancer cell viability. Thus, PAN-811 can be a potent drug candidate for chemotherapy-induced cognitive impairment.


Assuntos
Transtornos Cognitivos , Neoplasias/tratamento farmacológico , Síndromes Neurotóxicas , Piridinas/efeitos adversos , Espécies Reativas de Oxigênio/metabolismo , Tiossemicarbazonas/efeitos adversos , Animais , Linhagem Celular Tumoral , Transtornos Cognitivos/induzido quimicamente , Transtornos Cognitivos/metabolismo , Transtornos Cognitivos/patologia , Humanos , Camundongos , Neoplasias/metabolismo , Neoplasias/patologia , Síndromes Neurotóxicas/metabolismo , Síndromes Neurotóxicas/patologia , Piridinas/farmacologia , Tiossemicarbazonas/farmacologia
6.
Int J Mol Sci ; 14(12): 24438-75, 2013 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-24351827

RESUMO

Living cells continually generate reactive oxygen species (ROS) through the respiratory chain during energetic metabolism. ROS at low or moderate concentration can play important physiological roles. However, an excessive amount of ROS under oxidative stress would be extremely deleterious. The central nervous system (CNS) is particularly vulnerable to oxidative stress due to its high oxygen consumption, weakly antioxidative systems and the terminal-differentiation characteristic of neurons. Thus, oxidative stress elicits various neurodegenerative diseases. In addition, chemotherapy could result in severe side effects on the CNS and peripheral nervous system (PNS) of cancer patients, and a growing body of evidence demonstrates the involvement of ROS in drug-induced neurotoxicities as well. Therefore, development of antioxidants as neuroprotective drugs is a potentially beneficial strategy for clinical therapy. In this review, we summarize the source, balance maintenance and physiologic functions of ROS, oxidative stress and its toxic mechanisms underlying a number of neurodegenerative diseases, and the possible involvement of ROS in chemotherapy-induced toxicity to the CNS and PNS. We ultimately assess the value for antioxidants as neuroprotective drugs and provide our comments on the unmet needs.


Assuntos
Doenças Neurodegenerativas/metabolismo , Estresse Oxidativo , Animais , Antioxidantes/metabolismo , Antioxidantes/uso terapêutico , Apoptose , Estresse do Retículo Endoplasmático , Humanos , Doenças Neurodegenerativas/tratamento farmacológico , Doenças Neurodegenerativas/patologia , Oxirredutases/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Resposta a Proteínas não Dobradas
7.
J Alzheimers Dis ; 17(3): 611-9, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19433896

RESUMO

Oxidative stress plays a significant role in neurotoxicity associated with a variety of neurodegenerative diseases including Alzheimer's disease (AD). Increased oxidative stress has been shown to be a prominent and early feature of vulnerable neurons in AD. Olfactory neuroepithelial cells are affected at an early stage. Exposure to oxidative stress induces the accumulation of intracellular reactive oxygen species (ROS), which in turn causes cell damage in the form of protein, lipid, and DNA oxidations. Elevated ROS levels are also associated with increased deposition of amyloid-beta and formation of senile plaques, a hallmark of the AD brain. If enhanced ROS exceeds the basal level of cellular protective mechanisms, oxidative damage and cell death will result. Therefore, substances that can reduce oxidative stress are sought as potential drug candidates for treatment or preventative therapy of neurodegenerative diseases such as AD. PAN-811, also known as 3-aminopyridine-2-carboxaldehyde thiosemicarbazone or Triapine, is a small lipophilic compound that is currently being investigated in several Phase II clinical trials for cancer therapy due to its inhibition of ribonucleotide reductase activity. Here we show PAN-811 to be effective in preventing or reducing ROS accumulation and the resulting oxidative damages in both AD-derived and age-matched olfactory neuroepithelial cells.


Assuntos
Doença de Alzheimer/patologia , Células Neuroepiteliais/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Condutos Olfatórios/patologia , Estresse Oxidativo/efeitos dos fármacos , Piridinas/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Tiossemicarbazonas/farmacologia , Idoso , Envelhecimento/patologia , Análise de Variância , Estudos de Casos e Controles , Morte Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Líquido Extracelular/efeitos dos fármacos , Líquido Extracelular/metabolismo , Humanos , Peróxido de Hidrogênio/farmacologia , L-Lactato Desidrogenase/metabolismo , Oxidantes/farmacologia
8.
Neurosci Lett ; 422(1): 64-7, 2007 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-17600621

RESUMO

In an earlier study, we demonstrated that PAN-811 (3-aminopyridine-2-carboxaldehyde thiosemicarbazone), a novel neuroprotectant, provides protection against glutamate, staurosporine, veratridine, or hypoxia/hypoglycemia toxicities in primary cortical neuronal cultures by upregulating Bcl-2 expression [R.-W. Chen, C. Yao, X.C. Lu, Z.-G. Jiang, R. Whipple, Z. Liao, H.A. Ghanbari, B. Almassian, F.C. Tortella, J.R. Dave. PAN-811 (3-aminopyridine-2-carboxaldehyde thiosemicarbazone), a novel neuroprotectant, elicits its function in primary neuronal cultures by upregulating Bcl-2 expression. Neuroscience 135 (2005) 191-201]. Both JNK (c-Jun N-terminal kinase) and p38 MAP (mitogen-activated protein) kinase activation have a direct inhibitory action on Bcl-2 by phosphorylation. In the present study, we continued to explore the mechanism of PAN-811 neuroprotection. Our results indicate that treatment of cultured cortical neurons with glutamate (100 microM) induces phosphorylation of both JNK and p38 MAPK. Specifically, pretreatment of neurons with 10 microM PAN-811 (an optimal neuroprotective concentration) for 1h, 4h, or 24h significantly suppresses glutamate-mediated activation of both JNK and p38 MAPK. Furthermore, the p38 MAPK-specific inhibitor SB203580 and the JNK-specific inhibitor SP600125 prevented glutamate-induced neuronal death in these primary cultures. Our results demonstrate that glutamate-induced phosphorylation of JNK and p38 MAPK is suppressed by PAN-811, which might contribute to Bcl-2 upregulation and PAN-811 neuroprotection.


Assuntos
Antagonistas de Aminoácidos Excitatórios , Ácido Glutâmico/toxicidade , Proteínas Quinases JNK Ativadas por Mitógeno/antagonistas & inibidores , Fármacos Neuroprotetores/farmacologia , Piridinas/farmacologia , Tiossemicarbazonas/farmacologia , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores , Animais , Antracenos/farmacologia , Western Blotting , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Córtex Cerebral/citologia , Córtex Cerebral/efeitos dos fármacos , Feminino , Genes bcl-2/genética , Gravidez , Ratos , Ratos Sprague-Dawley , Sais de Tetrazólio , Tiazóis
9.
CNS Drug Rev ; 12(1): 77-90, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16834759

RESUMO

3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP) is a highly-hydrophobic small molecule that was originally developed for cancer therapy (Triapine, Vion Pharmaceuticals) due to its ability to inhibit ribonucleotide reductase, a key enzyme required for DNA synthesis. 3-AP has a high affinity for divalent cations, chelating the Fe(2+) at the R2 subunit of the enzyme and inhibiting formation of a tyrosyl radical essential for ribonucleotide reduction. We have demonstrated that 3-AP is also a potent neuroprotectant (as such, it is referred to as "PAN-811"). In vitro it completely blocks ischemic neurotoxicity at a concentration of 0.5 microM (EC(50) approximate, equals 0.35 microM) and hypoxic toxicity at 1.2 microM (EC(50) approximate, equals 0.75 microM). Full protection of primary cortical and striatal neurons can be achieved with 3-AP when it is added to the medium at up to six hours after an ischemic insult. 3-AP also suppresses cell death induced by neurotoxic agents, including staurosporine, veratridine and glutamate, indicating activity against a central target(s) in the neurodegenerative process. 3-AP acts via neutralization of two important intracellular effectors of excitatory neurotoxicity; calcium and free radicals. Its reported ability to elevate anti-apoptotic proteins is likely to be a consequence of the suppression of excessive intracellular free calcium. In a rat model of transient ischemia, a single bolus delivery of 3-AP 1 h after the initiation of ischemic attack reduced infarct volume by 59% when administered i.c.v. (50 mug per rat) and by 35% when administered i.v. (1 mg/kg). In Phase I clinical trials in cancer therapy 3-AP had no cardiovascular, CNS or other major adverse effects. Thus, 3-AP has a high potential for development as a novel, potent neuroprotectant for the treatment of neurodegenerative diseases.


Assuntos
Analgésicos/uso terapêutico , Encefalopatias/prevenção & controle , Neoplasias/tratamento farmacológico , Fármacos Neuroprotetores/uso terapêutico , Piridinas/uso terapêutico , Tiossemicarbazonas/uso terapêutico , Analgésicos/química , Analgésicos/farmacologia , Animais , Encefalopatias/etiologia , Encefalopatias/patologia , Morte Celular/efeitos dos fármacos , Humanos , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/química , Piridinas/química , Piridinas/farmacologia , Tiossemicarbazonas/química , Tiossemicarbazonas/farmacologia
10.
Proc Natl Acad Sci U S A ; 103(5): 1581-6, 2006 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-16423893

RESUMO

Cellular and molecular pathways underlying ischemic neurotoxicity are multifaceted and complex. Although many potentially neuroprotective agents have been investigated, the simplicity of their protective mechanisms has often resulted in insufficient clinical utility. We describe a previously uncharacterized class of potent neuroprotective compounds, represented by PAN-811, that effectively block both ischemic and hypoxic neurotoxicity. PAN-811 disrupts neurotoxic pathways by at least two modes of action. It causes a reduction of intracellular-free calcium as well as free radical scavenging resulting in a significant decrease in necrotic and apoptotic cell death. In a rat model of ischemic stroke, administration of PAN-811 i.c.v. 1 h after middle cerebral artery occlusion resulted in a 59% reduction in the volume of infarction. Human trials of PAN-811 for an unrelated indication have established a favorable safety and pharmacodynamic profile within the dose range required for neuroprotection warranting its clinical trial as a neuroprotective drug.


Assuntos
Infarto da Artéria Cerebral Média/tratamento farmacológico , Isquemia , Doenças Neurodegenerativas/tratamento farmacológico , Fármacos Neuroprotetores/farmacologia , Piridinas/farmacologia , Tiossemicarbazonas/farmacologia , Animais , Apoptose , Western Blotting , Cálcio/metabolismo , Córtex Cerebral/metabolismo , Quelantes/farmacologia , Técnicas de Cocultura , Corpo Estriado/metabolismo , Fragmentação do DNA , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Fluoresceínas/farmacologia , Sequestradores de Radicais Livres/metabolismo , Humanos , Hipóxia , L-Lactato Desidrogenase/metabolismo , Masculino , Necrose , Neurônios/metabolismo , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio , Fatores de Tempo
11.
Free Radic Biol Med ; 38(6): 746-54, 2005 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-15721985

RESUMO

Several recent studies support a link between tau protein phosphorylation and adduction of tau by reactive carbonyls. Indeed, the phosphorylation-dependent adduction of tau by carbonyl products resulting from lipid peroxidation creates the neurofibrillary tangle-related antigen, Alz50. To determine whether epitopes of carbonyl-modified tau are major conformational changes associated with neurofibrillary tangle formation, we examined seven distinct antibodies raised against neurofibrillary tangles that recognize unique epitopes of tau in Alzheimer disease. Consistently, all seven antibodies recognize tau more strongly (4- to 34-fold) after treatment of normal tau with the reactive carbonyl, 4-hydroxy-2-nonenal (HNE), but only when tau is in the phosphorylated state. These findings not only support the idea that oxidative stress is involved in neurofibrillary tangle formation occurring in brains of Alzheimer disease patients, but also show, for the first time, that HNE modifications of tau promote and contribute to the generation of the major conformational properties defining neurofibrillary tangles.


Assuntos
Doença de Alzheimer/imunologia , Proteínas tau/química , Proteínas tau/metabolismo , Idoso , Idoso de 80 Anos ou mais , Aldeídos/química , Doença de Alzheimer/metabolismo , Animais , Epitopos/química , Humanos , Imuno-Histoquímica , Peroxidação de Lipídeos , Camundongos , Modelos Genéticos , Estresse Oxidativo , Fosforilação , Conformação Proteica , Fatores de Tempo
13.
Aging Cell ; 3(1): 41-4, 2004 02.
Artigo em Inglês | MEDLINE | ID: mdl-14965355

RESUMO

Oxidative abnormalities precede clinical and pathological manifestations of Alzheimer's disease and are the earliest pathological changes reported in the disease. The olfactory pathways and mucosa also display the pathological features associated with Alzheimer's disease in the brain. Olfactory neurons are unique because they can undergo neurogenesis and are able to be readily maintained in cell culture. In this study, we examined neuronal cell cultures derived from olfactory mucosa of Alzheimer's disease and control patients for oxidative stress responses. Levels of lipid peroxidation (hydroxynonenal), N(epsilon)-(carboxymethyl)lysine (glycoxidative and lipid peroxidation), and oxidative stress response (heme oxygenase-1) were measured immunocytochemically. We found increased levels for all the oxidative stress markers examined in Alzheimer's disease neurons as compared to controls. Interestingly, in one case of Alzheimer's disease, we found hydroxynonenal adducts accumulated in cytoplasmic lysosome-like structures in about 20% of neurons cultured, but not in neurons from control patients. These lysosome-like structures are found in about 100% of the vulnerable neurons in brains of cases of Alzheimer's disease. This study suggests that manifestations of oxidative imbalance in Alzheimer's disease extend to cultured olfactory neurons. Primary culture of human olfactory neurons will be useful in understanding the mechanism of oxidative damage in Alzheimer's disease and can even be utilized in developing therapeutic strategies.


Assuntos
Doença de Alzheimer/patologia , Lisina/análogos & derivados , Neurônios/ultraestrutura , Mucosa Olfatória/citologia , Estresse Oxidativo , Aldeídos/metabolismo , Doença de Alzheimer/metabolismo , Linhagem Celular , Células Cultivadas , Heme Oxigenase (Desciclizante)/metabolismo , Heme Oxigenase-1 , Humanos , Imuno-Histoquímica , Peroxidação de Lipídeos , Lisina/metabolismo , Proteínas de Membrana , Neurônios/química , Neurônios/patologia
14.
Acta Neuropathol ; 105(5): 524-8, 2003 May.
Artigo em Inglês | MEDLINE | ID: mdl-12677454

RESUMO

Despite their terminally differentiated status, vulnerable neurons in Alzheimer's disease (AD) display evidence of cell cycle activation, suggesting that mitotic dysfunction may be important in disease pathogenesis. To further delineate the role of mitotic processes in disease pathogenesis, we investigated phosphorylated histone H3, a key component involved in chromosome compaction during cell division. Consistent with an activation of the mitotic machinery, we found an increase in phosphorylated histone H3 in hippocampal neurons in AD. However, rather than within the nucleus as in actively dividing cells, activated phosphorylated histone H3 in AD is restricted to the neuronal cytoplasm despite activation of the mitotic machinery. Therefore, the aberrant cytoplasmic localization of phosphorylated histone H3 indicates a mitotic catastrophe that leads to neuronal dysfunction and neurodegeneration in AD.


Assuntos
Doença de Alzheimer/metabolismo , Histonas/metabolismo , Mitose , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/patologia , Estudos de Casos e Controles , Feminino , Hipocampo/metabolismo , Humanos , Immunoblotting , Imuno-Histoquímica , Masculino , Fragmentos de Peptídeos , Fosforilação , Células Piramidais/metabolismo
15.
Neurosignals ; 11(5): 282-92, 2002.
Artigo em Inglês | MEDLINE | ID: mdl-12566929

RESUMO

Selective neurodegeneration is a prominent feature in Alzheimer's disease; however, the mechanism of neuronal death is still unclear. Nonetheless, the topographical distribution of different types of receptors is thought to contribute to the regional selective nature of neuronal degeneration. Specifically, since glutamatergic transmission is severely altered by the early degeneration of cortico-cortical connections and hippocampal projections in Alzheimer's disease, we suspect that glutamate receptors may play a new role in the pathophysiology of disease. Here we review the salient aspects of glutamate receptor expression in Alzheimer's disease and how their differential regulation can contribute to the selective neurodegeneration seen in the disease. Additionally, we assess the potential therapeutic value of glutamate receptors as a target for drug intervention in Alzheimer's disease.


Assuntos
Doença de Alzheimer/patologia , Doenças Neurodegenerativas/patologia , Receptores de Glutamato/fisiologia , Doença de Alzheimer/fisiopatologia , Animais , Encéfalo/patologia , Encéfalo/fisiopatologia , Humanos , Modelos Neurológicos , Doenças Neurodegenerativas/fisiopatologia , Receptores de Ácido Caínico/fisiologia , Receptores de N-Metil-D-Aspartato/fisiologia
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