Wyniki wyszukiwania

1

Molecular mediators, environmental modulators and experience-dependent synaptic dysfunction in Huntington's disease

100%

Hannan A. J.

Acta Biochimica Polonica

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2004

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tom 51

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nr 2

Huntington's disease (HD) is an autosomal dominant disorder in which there is progressive neurodegeneration producing motor, cognitive and psychiatric symptoms. HD is caused by a trinucleotide (CAG) repeat mutation, encoding an expanded polyglutamine tract in the huntingtin protein. At least eight other neurodegenerative diseases are caused by CAG/glutamine repeat expansions in different genes. Recent evidence suggests that environmental factors can modify the onset and progression of Huntington's disease and possibly other neurodegenerative disorders. This review outlines possible molecular and cellular mechanisms mediating the polyglutamine-induced toxic 'gain of function' and associated gene-environment interactions in HD. Key aspects of pathogenesis shared with other neurodegenerative diseases may include abnormal protein-protein interactions, selective disruption of gene expression and 'pathological plasticity' of synapses in specific brain regions. Recent discoveries regarding molecular mechanisms of pathogenesis are guiding the development of new therapeutic approaches. Knowledge of gene-environment interactions, for example, could lead to development of ‘enviromimetics’ which mimic the beneficial effects of specific environmental stimuli. The effects of environmental enrichment on brain and behaviour will also be discussed, together with the general implications for neuroscience research involving animal models.

2

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Caring for patients with Huntington disease - a survey of caregivers’ experiences and views

84%

Domaradzki J.

Journal of Pre-Clinical and Clinical Research

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2015

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tom 09

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nr 2

Introduction. Despite the growing interest in the consequences of caring for patients with Huntington disease (pHD), little is known about the family caregivers of such patients in Poland. Identification of their needs can improve caregivers’ wellbeing, the quality of care and condition of pHD. The aim of this study was to understand the social functioning of family caregivers of pHD and their perception of the caregiving role. Materials and methods. Data was collected from 55 family caregivers of pHD. A structured questionnaire was used consisting of 86 questions subsumed into five domains: ‘Problems’ and ‘Feelings related to caregiving’, ‘Attitude toward caregiving’, ‘Satisfaction with life’ and ‘Perception of healthcare services’. Correlations between the different scales and other characteristics were measured as potential predictors of the burden. Non-parametric statistical methods were used in the analysis. Results. Most respondents experienced a high (50.9%) or moderate (30.95%) feeling of burden. Although 70.9% of caregivers perceived caregiving positively, for many it was a source of negative feelings. Only 10.9% of respondents declared that caregiving decreased their QoL. Carers’ perception of caregiving was mostly influenced by their negative experiences with the healthcare system. Respondents’ domicile, religious practices, age, income, marital status, time of diagnosis and of caregiving, patient’s age and stage of disease also influenced their experiences. Conclusions. Health professionals and policy planners should focus on monitoring caregivers’ health, identifying their needs, sources of distress, and supporting caregivers’ coping strategies. They should also be better educated about the clinical and practical aspects of HD.

3

Circadian rhythms of melatonin and cortisol in manifest Huntington's disease and in acute cortical ischemic stroke

84%

Adamczak-Ratajczak A., Kupsz J., Owecki M., Zielonka D., Sowinska A., Checinska-Maciejewska Z., Krauss H., Michalak S., Gibas-Dorna M.

Journal of Physiology and Pharmacology

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2017

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tom 68

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nr 4

4

"Understand and describe life" - scientific conference

84%

BioTechnologia. Journal of Biotechnology Computational Biology and Bionanotechnology

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2024

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tom 105

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nr 1

5

Neurodegenerative aspects of protein aggregation

84%

Trzesniewska K., Brzyska M., Elbaum D.

Acta Neurobiologiae Experimentalis

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2004

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tom 64

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nr 1

6

Role of brain glutamic acid metabolism changes in neurodegenerative pathologies

67%

Kanunnikova N. P.

Journal of Biology and Earth Sciences

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2012

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tom 02

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nr 1

7

Importance of cannabinoids in the functioning of the central nervous system

67%

Wroblewska-Luczka P., Florek-Luszczki M., Luszczki J. J.

Health Problems of Civilization

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2018

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tom 12

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nr 3

At present, there is a great emphasis of public opinion on the legalisation of medical marijuana, i.e. the top parts of the cannabis plants rich in tetrahydrocannabinol (THC). Nevertheless, in the cannabis plants, there are many various cannabinoids, including cannabidiol (CBD). Scientific reports to-date indicate the possibility for using pharmacologically active cannabinoids in the treatment of such diseases/symptoms as: anorexia, vomiting, neuropathic pain, inflammatory diseases, multiple sclerosis, degenerative diseases of the central nervous system (Parkinson’s disease, Huntington’s disease, Alzheimer’s disease, Tourette’s syndrome), epilepsy, schizophrenia, and obesity. The article presents up-to-date information on the results of experimental studies concerning the effectiveness of cannabinoids, with particular consideration of diseases related with the central nervous system, including epilepsy, neuropathic pain, mental disorders, as well as obesity and anorexia.

8

P2X7 receptor signaling pathway as a therapeutic target for neurodegenerative diseases

67%

Takenouchi T., Sekiyama K., Sekigawa A., Fujita M., Waragai M., Sugama S., Iwamaru Y., Kitani H., Hashimoto M.

Archivum Immunologiae et Therapiae Experimentalis

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2010

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tom 58

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nr 2

91-96

9

In search for effective modulators of the proteasome activity

67%

Karpowicz P., Stoj J., Gaczynska M., Osmulski P., Jankowska E.

Acta Neurobiologiae Experimentalis

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2013

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tom 73

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nr 1

Proteasome is a multi-activity enzyme involved in a ubiquitin-dependent turnover of cytoplasmic and nuclear proteins. It recognizes and digests short-lived regulatory proteins, influencing cellular processes as crucial as progression of the cell cycle, transcription, oncogenesis and flux of substrates through metabolic pathways. The enzyme is responsible also for the housekeeping chores, degrading misfolded or oxidatively damaged proteins. Defects in the proteasome action play a causal role in development of a number of diseases, among which are cerebral ischemia and neurodegenerative disorders such as Huntington’s, Alzheimer’s, and Parkinson’s diseases. Being a multifunctional proteolytic machinery, the proteasome must act under a strict control to prevent massive degradation of all intracellular proteins, which would result in a cell death. One of the levels of such a control is the proteasome structure itself. The core particle called 20S proteasome is a barrel-like structure made up of four rings of seven subunits each. The outer (α) rings play predominantly a structural role forming a kind of a gated channel leading to the proteolytic chamber. The inner-β-rings harbor six active sites, concealed inside the cavity formed by the β subunits. So far, the only proteasome-targeting agents used in clinics are competitive inhibitors, directly blocking the enzyme’s active sites. However, the multi-subunit barrel-like structure of the 20S proteasome encourages to test compounds which can target allosteric interactions between subunits and influence the gating mechanism, involved in the control of the substrates’ uptake. Such modulators may provide a precise and substrate-specific regulation of the proteasome catalytic performance. Additionally, targeting the allosteric interactions may enable not only inhibition but also stimulation of the proteasome, which is crucial in managing disorders connected with the proteasome not sufficient activity, such as neurodegenerative diseases. A variety of protein ligands, interacting with the outer ring of the 20S proteasome and modulating its activity, is already known. They can serve as templates for design of putative small-molecule allosteric drugs. In an effort to find synthetic compounds able to enhance or suppress the performance of the proteasome active centers we utilize one of such protein ligands – HIV-1 Tat protein. The protein is known to inhibit the core proteasome and to interfere with the physiological PA28 activator in its binding to the 20S. G48RKKRRQRRRPS59 fragment of HIV-1 Tat (Tat1) occurred to be very efficient in the 20S proteasome inhibition. By single and multiple alanine substitutions we have recognized “hot spots” in the sequence of Tat1. NMR and molecular dynamics calculations allowed us to correlate these putative pharmacophores with the structural turns. By introduction of a non-peptide turn-inducing modification to the Tat1 sequence we have obtained the derivatives highly toxic for human cultured cancer cells HeLa.S3. The work was supported by grants: NCN 2011/01/B/ST5/06616 and DS/8440-4-0172-2

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Synthesis, physicochemical and biological properties of poly-alpha-amino acids - the simplest of protein models

67%

Katchalski-Katzir E.

Acta Biochimica Polonica

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1996

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tom 43

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nr 1

During the 1950s, linear and multichain poly-a-amino acids were synthesized by polymerization of the corresponding N-carboxy-amino acid anhydrides in solution in the presence of suitable catalysts. The resulting homo- and heteropolymers have since been widely employed as simple protein models. Under appropriate conditions, poly-a-amino acids, in the solid state and in solution, were found to acquire conformations of an a-helix and of (^-parallel and antiparallel pleated sheets, or to exist as random coils. Their use in experimental and theoretical investigations of helix-coil transitions helped to shed new light on the mechanisms involved in protein denaturation. Poly-a-amino acids played an important role in the deciphering of the genetic code. In addition, analysis of the antigenicity of poly-a-amino acids led to the elucidation of the factors determining the antigenicity of proteins and peptides. Interest in the biological and physicochemical characteristics of poly-a-amino acids was recently renewed because of the reported novel findings that some copolymers of amino acids are effective as drugs in multiple sclerosis, and that glutamine repeats and reiteration of other amino acids occur in inherited neurodegenerative diseases. The presence of repeating sequences of amino acids in proteins, and of nucleotides in DNA, raises many interesting questions about their respective roles in determining protein structure and function, and gene performance and regulation.

11

Gene expression in neuronal apoptosis - looking for a therapeutic window

67%

Figiel I., Filipkowski R. K., Hetman M., Kaminska B., Kaczmarek L.

Biotechnologia

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1996

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nr 4

Ograniczanie wyników

Molecular mediators, environmental modulators and experience-dependent synaptic dysfunction in Huntington's disease

Caring for patients with Huntington disease - a survey of caregivers’ experiences and views

Circadian rhythms of melatonin and cortisol in manifest Huntington's disease and in acute cortical ischemic stroke

"Understand and describe life" - scientific conference

Neurodegenerative aspects of protein aggregation

Role of brain glutamic acid metabolism changes in neurodegenerative pathologies

Importance of cannabinoids in the functioning of the central nervous system

P2X7 receptor signaling pathway as a therapeutic target for neurodegenerative diseases

In search for effective modulators of the proteasome activity

Synthesis, physicochemical and biological properties of poly-alpha-amino acids - the simplest of protein models

Gene expression in neuronal apoptosis - looking for a therapeutic window