Wyniki wyszukiwania - Biblioteka Nauki

1

Purine nucleoside analogs in the therapy of cancer and neuroinflammation

100%

Savić D. , Stanković T. , Lavrnja I. , Podolski-Renić A. , Banković J. , Peković S. , Stojiljković M. , Rakić L. , Ruždijić S. , Pešić M.

Molecular inhibitors in targeted therapy

|

2015

|

tom 1

|

nr 1

EN

Purine nucleoside analogs have been in clinical use for almost 50 years. At the beginning developed as antiviral agents, later their efficacy was demonstrated in cancer treatment, especially hematological malignances. The approval of new purine nucleoside analogs by US Food and Drug Administration (FDA) over the past decade implies that the interest for these drugs still exists. Here, we review new nucleoside analogs that are currently in preclinical or clinical development as anticancer agents. In addition, we highlight the potential for implementation of these drugs in other pathological conditions, particularly in neuroinflammation.

2

Immunologiczne aspekty choroby Alzheimera

75%

Wojtera M. , Kłoszewska I. , Sobów T. , Liberski P. P.

Aktualności Neurologiczne

|

2006

|

tom 6

|

nr 2

108-115

EN

Alzheimer’s disease (AD) is an incurable neurodegenerative disease, which is accompanied by chronic inflammation. The immune system has an important role in the process of the disease. The deposition of amyloid β (Aβ) protein is a key pathological feature in Alzheimer’s disease. This article reviews immunotherapeutic strategies against AD. In murine models of AD, both active and passive immunization against Aβ induces a marked reduction in an amyloid brain burden and an improvement in cognitive functions. The findings from murine studies lead to clinical studies. One Phase II clinical trial of active immunization against Aβ was discontinued after 18 patients developed meningoencephalitis. After this lesson learned, new immunotherapeutic strategies, including both active and passive immunization, are investigated in clinical centers.

PL

Choroba Alzheimera (AD) jest nieuleczalną chorobą neurodegeneracyjną, której towarzyszy przewlekły proces zapalny. Układ immunologiczny może mieć istotny wpływ na przebieg procesu chorobowego. Głównym patologicznym wyznacznikiem choroby Alzheimera jest gromadzenie w obrębie mózgu złogów β-amyloidu. W obecnym artykule przedstawiono informacje na temat możliwości zastosowania immunoterapii w leczeniu choroby Alzheimera. Metody immunoterapeutyczne, mające usuwać amyloid β z chorych mózgów, dały bardzo pozytywne rezultaty w badaniach na zwierzętach. Zarówno metody aktywnej, jak i biernej immunizacji powodowały wyraźne zmniejszenie zawartości amyloidu w mózgach myszy transgenicznych oraz poprawę ich funkcji poznawczych. Bardzo dobre wyniki na modelach zwierzęcych pozwoliły przeprowadzić wstępne badania kliniczne. Ich wyniki są również obiecujące, choć obarczone ryzykiem zapalenia mózgu. Jedyne dotychczas badanie II Fazy z zastosowaniem szczepionki przeciwko Aβ zostało przerwane z powodu rozwoju u 18 pacjentów zapalenia opon mózgowych i mózgu. Obecnie ośrodkach badawczych pojawiają się nowe rodzaje technik immunoterapeutycznych.

3

Central nervous system and peripheral expression of CCL19, CCL21 and their receptor CCR7 in experimental model of multiple sclerosis

75%

Bielecki B. , Jatczak-Pawlik I. , Wolinski P. , Bednarek A. , Glabinski A.

Archivum Immunologiae et Therapiae Experimentalis

|

2015

|

tom 63

|

nr 5

4

Dynamics of expression of the mRNA for cytokines and inducible nitric synthase in a murine model of the Parkinson's disease

63%

Ciesielska A. , Joniec I. , Przybylkowski A. , Gromadzka G. , Kurkowska-Jastrzebska I. , Czlonkowska A. , Czlonkowski A.

Acta Neurobiologiae Experimentalis

|

2003

|

tom 63

|

nr 2

5

Glutamate receptors antagonists attenuate neurological deficits and modulate neuroinflammation in Lewis rat subjected to experimental autoimmune encephalomyelitis

51%

Sulkowski G. , Dabrowska-Bouta B. , Chalimoniuk M. , Lenkiewicz A. , Struzynska L.

Acta Neurobiologiae Experimentalis

|

2013

|

tom 73

|

nr 1

EN

Experimental autoimmune encephalomyelitis (EAE) is an animal model that mimics many aspects of multiple sclerosis (MS). Chronic or relapsing inflammation of the central nervous system results in the destruction of myelin sheath and cytokines play an important role in the pathogenesis of both MS and EAE. Myelin, oligodendrocytes and neurons are lost due to an inflammatory attack by leukocytes infiltrating the central nervous system (CNS) and releasing cytotoxic cytokines, anti CNS antibodies and large amounts of the excitatory neurotransmitter glutamate. Pharmacological studies have suggested that glutamate receptors mediate white matter injury in a variety of CNS diseases, including multiple sclerosis (MS). Memantine and amantadine are ionotropic glutamate receptors (iGluRs) antagonists. Memantine, a clinically applied drug with N-methyl-D-aspartate (NMDA) receptor antagonistic effects, dose-dependently ameliorates neurological deficits in Lewis rats subjected to experimental autoimmune encephalomyelitis (EAE). The aim of the present study was to investigate the effects of memantine and amantadine on the expression of proinflammatory cytokines such interleukin 1beta (IL-1β), interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α) and various chemokines in the brain of EAE rats. Real-time Reverse Transcription-Polymerase Chain Reaction (RT-PCR) and Western Blot were used to analyze the cytokine profile. We noticed increased expression of array of cytokines in experimental group when compared to the control. Dramatic increase of IL-1β, IL-6, TNF-α, and chemokines concentration corresponding to the intensity of neurological symptoms and loss of weight was observed in EAE rats. Administration of iGluR antagonists at an advanced stage of unremitting EAE resulted in amelioration of the disease. Cytokine analysis revealed that memantine significantly decreased the expression of interleukins: IL-6 (65%), IL-1β (60%) and TNF-α (45%) whereas treatment with amantadine reduced only the expression of IL-6 (60%) and TNF-α (15%) when compared to EAE animals. These results show that antagonists of iGlu receptors modulate the course of the disease by reducing the expression of proinflammatory cytokines thereby confirming the involvement of glutamate receptors into pathological mechanisms operating during EAE. This study was supported by grant nr NN401620038 from Polish Ministry of Science and Higher Education

6

Mitochondrial integrity and function in model systems of CNS diseases

51%

Culmsee C.

Acta Neurobiologiae Experimentalis

|

2019

|

tom 79

|

nr Suppl.1

EN

Mitochondria are key regulators of energy metabolism, redox balance, calcium homeostasis, and programmed cell death. In the past, we characterized mitochondria acting as targets of both caspase-dependent and caspase- independent death signalling triggered by increased oxidative stress and as executioners of programmed death signalling in neurons. For example, we identified mitochondrial damage in caspase‑independent neuronal death after cerebral ischemia in vivo, and in oxidative cell death, i.e., ferroptosis in vitro. Protective intervention against oxidative damage further confirmed the conclusion that mitochondria represent the “point of no return” in caspase‑independent paradigms of programmed cell death. Further, we found more recently that mitochondri al-targeted alpha-synuclein caused severe mitochondrial toxicity and caspase-dependent cell death in human dopaminergic neurons, a model system relevant to Parkinson’s disease. In different model systems of neuronal death, neuroprotective interference with mitochondrial pathways of programmed cell death was frequently attributed to metabolic switches, i.e., reduced mitochondrial respiration and increased glycolytic activity. Accordingly, targeting metabolic switches may serve as a general strategy for mitochondrial protection and, thereby, neuroprotection, but may also affect mechanisms of neuroinflammation involving activation of microglia. The understanding of the underlying mechanism of such metabolic protection may reveal novel therapeutic targets in neural diseases featuring mitochondrial impairments and neuroinflammation.

7

The classification of microglial activation phenotypes on neurodegeneration and regeneration in Alzheimer’s disease brain

51%

Varnum M. M. , Ikezu T.

Archivum Immunologiae et Therapiae Experimentalis

|

2012

|

tom 60

|

nr 4