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| 2. |
- Andreasen, Niels, et al.
(författare)
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Amyloid-related biomarkers for Alzheimer's disease.
- 2008
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Ingår i: Current medicinal chemistry. - : Bentham Science Publishers Ltd.. - 0929-8673. ; 15:8, s. 766-71
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Forskningsöversikt (refereegranskat)abstract
- Alzheimer's disease (AD) is an age-related disorder that causes brain damage resulting in progressive cognitive impairment and death. Three decades of progress have given us a detailed understanding of the underlying molecular mechanisms. Over the past 10 years, this knowledge has translated into a range of targets for therapy, the most promising of which is amyloid beta (Abeta). An imbalance between the production and clearance of Abeta is thought by many to represent the earliest event in the pathogenesis of AD. Abeta is known to be subject to oligomerisation, a process that increases its synaptotoxicity. The oligomers may aggregate further to proto-fibrils and fibrils, eventually forming senile plaques, the neuropathological hallmark of AD. In this article we review the key aspects of Abeta as a biomarker for AD, including its pathogenicity, the diagnostic performance of different Abeta assays in different settings, and the potential usefulness of Abeta as a surrogate marker for treatment efficacy in clinical trials of novel Abeta-targeting drugs.
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| 3. |
- Bjorklund, Geir, et al.
(författare)
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Metals and Parkinson's Disease : Mechanisms and Biochemical Processes
- 2018
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Ingår i: Current Medicinal Chemistry. - : Bentham Science Publishers Ltd.. - 0929-8673 .- 1875-533X. ; 25:19, s. 2198-2214
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Forskningsöversikt (refereegranskat)abstract
- Genetic background accounts for only 5 to 10% of the reported cases of Parkinson's disease (PD), while the remaining cases are of unknown etiology. It is believed that environmental factors may be involved in the causality of a large proportion of PD cases. Several PD genes are activated by xenobiotic exposure, and a link between pesticide exposure and PD has been demonstrated. Many epidemiological studies have shown an association between PD and exposure to metals such as mercury, lead, manganese, copper, iron, aluminum, bismuth, thallium, and zinc. This review explores the biological effects, the pathogenetic processes, genetic susceptibilities to metals as well as examining future strategies for PD treatment, such as chelation therapy.
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| 4. |
- Carlsson, Maria L., 1959, et al.
(författare)
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Schizophrenia: from dopamine to glutamate and back.
- 2004
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Ingår i: Current medicinal chemistry. - 0929-8673. ; 11:3, s. 267-77
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Tidskriftsartikel (refereegranskat)abstract
- The first part of the present review describes the exciting journey of dopamine stabilizers, starting in the early eighties with the development of the partial dopamine agonist (-)-3-PPP of phenylpiperidine structure, via various compounds with aminotetraline structure with preferential autoreceptor antagonist properties, and then back again to phenylpiperidine compounds carrying substituents on the aromatic ring that transformed them from partial dopamine agonists to partial dopamine receptor antagonists, such as OSU6162. OSU6162 was brought to the clinic and has in preliminary trials showed antidyskinetic and antipsychotic efficacy. The second part of this review describes results from a hypoglutamatergia mouse model for cognitive symptoms of schizophrenia, where we have tested traditional neuroleptics, new generation antipsychotics with marked 5-HT2 vs dopamine D2 receptor blockade as well as a dopamine stabilizer belonging to the partial dopamine receptor antagonist category.
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| 6. |
- Ekström, Per, et al.
(författare)
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Novel In Situ Activity Assays for the Quantitative Molecular Analysis of Neurodegenerative Processes in the Retina
- 2014
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Ingår i: Current Medicinal Chemistry. - : Bentham Science Publishers Ltd.. - 0929-8673. ; 21:30, s. 3478-3493
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Tidskriftsartikel (refereegranskat)abstract
- The mechanisms of neuronal cell death are still only poorly understood, which has hindered the advancement of therapies for many currently untreatable neurodegenerative diseases. This calls for the development of new methods which reveal critical molecular mechanisms of the celldeath machinery with both high sensitivity and cellular resolution. Using animal models for hereditary neurodegeneration in the retina, we have developed or adapted different biochemical assays to determine the enzymatic activities of calpain, poly-ADP-ribose-polymerase (PARP), and histone deacetylase (HDAC) directly and in situ. Additionally, the enzymatic activity of cGMP-dependent protein kinase (PKG) was assessed indirectly using in situ immunohistological techniques to detect PKG-activity-dependent products. Combining these assays with in situ cell death markers revealed close temporospatial correlations, suggesting causal connections between the PKG, HDAC, PARP and calpain activities and neuronal cell death. Using different pharmacological and genetic manipulations, causality could indeed be demonstrated. Surprisingly, the often dramatic rises in metabolic activities didnot match by corresponding increases in expression, highlighting the importance of analyses of protein activities at the cellular level. The above mentioned studies identified a number of metabolic processes previously unknownto be involved in inherited retinal degeneration. Comparing different animal retinal degeneration models uncovered striking similarities in enzymatic activities, suggesting a generality of the destructive pathways. Taken together, these findings provided a number of novel targets for neuroprotection and as such opened up new perspectives for the therapy of hereditary neurodegeneration in the retina and possibly other parts of the central nervous system.
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| 7. |
- El-Seedi, Hesham R., et al.
(författare)
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Naturally Occurring Xanthones; Biological Activities, Chemical Profiles and In Silico Drug Discovery
- 2024
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Ingår i: Current Medicinal Chemistry. - : Bentham Science Publishers Ltd.. - 0929-8673 .- 1875-533X. ; 31:1, s. 62-101
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Forskningsöversikt (refereegranskat)abstract
- Xanthones are widely distributed polyphenols, present commonly in higher plants; Garcinia, Calophyllum, Hypericum, Platonia, Mangifera, Gentiana and Swertia. Xanthone tricyclic scaffold is able to interact with different biological targets, showing antibacterial and cytotoxic effects, as well as potent effects against osteoarthritis, malaria, and cardiovascular diseases. Thus, in this article we focused on pharmacological effects, applications and preclinical studies with the recent updates of xanthon & PRIME;s isolated compounds from 2017-2020. We found that only a-mangostin, gambogic acid, and mangiferin, have been subjected to preclinical studies with particular emphasis on the development of anticancer, diabetes, antimicrobial and hepatoprotective therapeutics. Molecular docking calculations were performed to predict the binding affinities of xanthone-derived compounds against SARS-CoV-2 M-pro. According to the results, cratoxanthone E and morellic acid demonstrated promising binding affinities towards SARS-CoV-2 M-pro with docking scores of -11.2 and -11.0 kcal/mol, respectively. Binding features manifested the capability of cratoxanthone E and morellic acid to exhibit nine and five hydrogen bonds, respectively, with the key amino acids of the M-pro active site. In conclusion, cratoxanthone E and morellic acid are promising anti-COVID-19 drug candidates that warrant further detailed in vivo experimental estimation and clinical assessment.
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| 8. |
- El-Seedi, Hesham R., et al.
(författare)
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Naturally occurring xanthones; latest investigations : isolation, structure elucidation and chemosystematic significance
- 2009
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Ingår i: Current Medicinal Chemistry. - : Bentham Science Publishers Ltd.. - 0929-8673 .- 1875-533X. ; 16:20, s. 2581-2626
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Forskningsöversikt (refereegranskat)abstract
- In this review, an updated literature survey covering the reports of naturally occurring xanthones in the period of 2005-2008 is presented. In some 143 studies, the isolation of 264 different xanthones from 36 plant species (representing 15 genera in 6 families of higher plants), 7 species of fungi, and 1 lichen species were reported. Of these, 122 compounds were isolated for the first time from nature. We discuss plant origin, the way of separation, and spectral analysis done for structure elucidation, along with a brief discussion of the chemosystematic significance.
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| 9. |
- El-Seedi, Hesham R., et al.
(författare)
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Recent insights into the biosynthesis and biological activities of natural xanthones
- 2010
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Ingår i: Current Medicinal Chemistry. - : Bentham Science Publishers Ltd.. - 0929-8673 .- 1875-533X. ; 17:9, s. 854-901
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Forskningsöversikt (refereegranskat)abstract
- This review focuses on recent advances in our understanding of the complex biosynthetic pathways and diverse biological activities of naturally occurring xanthones. The biosynthesis section covers studies published from 1989 to 2008 on xanthone production in plants and fungi, while the bioactivity review presents tabulated activities of more than 250 xanthones described in studies published from 2001 to 2008, together with structural information and indications of their wide-ranging potential uses as pharmacological tools. A large number of relevant papers have been published on these subjects (128 cited here), illustrating the diversity of the xanthones and their possible uses.
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| 10. |
- Eriksson, Staffan
(författare)
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Is the Expression of Deoxynucleoside Kinases and 5 '-nucleotidases in Animal Tissues Related to the Biological Effects of Nucleoside Analogs?
- 2013
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Ingår i: Current Medicinal Chemistry. - : Bentham Science Publishers Ltd.. - 0929-8673 .- 1875-533X. ; 20, s. 4241-4248
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Tidskriftsartikel (refereegranskat)abstract
- Nucleoside analogs serve as important chemotherapeutic agents in a number of severe diseases such as cancer and viral infections. These agents are pro-drugs that have to be taken up and phosphorylated in several steps to be trapped in the cells and transformed to active metabolites that inhibit essential steps in the replication of viruses or malignant cells. The anabolic deoxynucleoside kinases (dNKs) and catabolic 5'- nucleotidases(5'-NTs) are involved in maintaining substrate cycles, and act as regulators for the intracellular pools of active nucleotide metabolites. In this chapter the expression patterns of the four dNKs i.e. cytosolic deoxycytidine kinase (dCK) and thymidine kinase 1 (TK1) and the mitochondrial thymidine kinase 2 (TK2) and deoxyguanosine kinase (dGK) as well as the six intracellular 5'-NTs: cN-IA, cN-IB, cN-II, cN-III, cdN, mdN, present in animal cells and tissues will be described. Their role as primary controllers of the accumulation and activation of important anti viral and anti cancer nucleoside analogs in different tissues involved in the pathophysiology of these diseases will be evaluated. The predictability of using the ratios between the activities of the dNKs and 5'-NTs for estimating efficacy and side effects of nucleoside drug candidates will be discussed as well as recommendations on how to use this information to improve future therapies with nucleoside drugs.
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