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    Wyświetlanie 1-9 z 9
    Tytuł:
    Wtrętowe zapalenie mięśni: objawy kliniczne, diagnostyczne parametry biopsji mięśniowej i rozważania patogenetyczne
    Inclusion-body myositis: clinical symptoms, diagnostic criteria of muscle biopsy and pathogenetic considerations
    Autorzy:
    Askanas, Valerie
    King Engel, W.
    Wójcik, Sławomir
    Powiązania:
    https://bibliotekanauki.pl/articles/1062113.pdf
    Data publikacji:
    2005
    Wydawca:
    Medical Communications
    Tematy:
    amyloid-β
    diagnostic criteria
    pathogenesis
    s-IBM
    sporadic inclusion-body myositis
    β-amyloid
    kryteria diagnostyczne
    wtrętowe zapalenie mięśni
    patogeneza
    Opis:
    Sporadic inclusion-body myositis (s-IBM), the most common muscle disease of older persons, is of unknown cause, and there is no successful treatment. Interest in sporadic inclusion-body myositis has been enhanced by the recent identification within the s-IBM muscle fibers of several abnormally accumulated proteins, which provides novel and important clues to the pathogenesis of this disorder. Here we summarize the clinical presentation, molecular phenotype, diagnostic criteria, and the newest advances related to seeking the pathogenic mechanism(s) of s-IBM. On the basis of our research, several processes seem to be important in relation to the still speculative pathogenesis: 1) increased transcription and accumulation of amyloid-β precursor protein (AβPP), and accumulation of its proteolytic fragment Aβ; 2) abnormal accumulation of cholesterol and its related protein; 3) oxidative stress; 4) accumulations of intramuscle fiber multiprotein aggregates; 5) increased accumulation of myostatin within the muscle fiber and 6) evidence that unfolded/misfolded proteins participate in s-IBM pathogenesis. Our basic hypothesis is that overexpression of AβPP within the aging muscle fibers is an early upstream event causing a subsequent pathogenic cascade.
    Wtrętowe zapalenie mięśni (s-IBM) jest najczęstszą chorobą mięśni szkieletowych występującą u starszych osób. Przyczyna tej choroby pozostaje nieznana i jak dotąd brak jest skutecznego leczenia. Na wzrost zainteresowania s-IBM wpłynęło przede wszystkim odkrycie wewnątrz włókien mięśniowych wielu nadmiernie/nieprawidłowo gromadzonych białek, co pozwoliło na wyciągnięcie nowych wniosków dotyczących patogenezy tej choroby. W poniższej pracy podsumowujemy obraz kliniczny, charakterystyczne zmiany patologiczne oraz kryteria diagnostyczne. Na bazie naszych doświadczeń wskazujemy również na kilka zjawisk, które wydają się szczególnie istotne w patogenezie s-IBM. Zaliczyć do nich należy: 1) zwiększoną transkrypcję i nadmierne gromadzenie białka prekursorowego β-amyloidu (AβPP) oraz gromadzenie jego fragmentu β-amyloidu; 2) nieprawidłowe gromadzenie cholesterolu i związanych z nim białek; 3) stres oksydacyjny; 4) gromadzenie wewnątrz włókien mięśniowych wielobiałkowych agregatów; 5) nadmierne gromadzenie miostatyny wewnątrz włókien mięśniowych oraz 6) dowody na to, że białka, które nie posiadają prawidłowej, natywnej konformacji, odgrywają rolę w patogenezie s-IBM. Zgodnie z naszą główną hipotezą nadmierna ekspresja AβPP wewnątrz starzejących się włókien mięśniowych zapoczątkowuje patogenetyczną kaskadę s-IBM.
    Źródło:
    Aktualności Neurologiczne; 2005, 5, 4; 244-254
    1641-9227
    2451-0696
    Pojawia się w:
    Aktualności Neurologiczne
    Dostawca treści:
    Biblioteka Nauki
    Artykuł
    Tytuł:
    Dobry amyloid β? Właściwości chemiczne peptydów Aβ4-x wskazują na ich znaczenie biologiczne
    Good β-amyloid? Chemical properties of Aβ4-x peptides indicate their biological relevance
    Autorzy:
    Bal, Wojciech
    Powiązania:
    https://bibliotekanauki.pl/articles/172163.pdf
    Data publikacji:
    2019
    Wydawca:
    Polskie Towarzystwo Chemiczne
    Tematy:
    peptydy β-amyloidowe
    choroba Alzheimera
    ATCUN/NTS
    wiązanie Cu(II)
    aktywność redoks
    amyloid β peptides
    Alzheimer’s disease
    Cu(II) binding
    redox reactivity
    Opis:
    Alzheimer’s Disease is a neurodegenerative condition, an irreversible progressive dementia caused by death of neurons in brain structures responsible for memory related processes. Despite many years of research and numerous trials, no therapy succeeded that could stop the development of this disease, which affects tens of millions of patients worldwide. The amyloid cascade prevails among a variety of possible mechanisms of its development proposed in the scientific literature. It proposes that death of neurons, preceded by dysfunction of their synaptic activity is caused by the incremental formation of structures (fibrils, oligomers) composed of Aβ peptides. In its copper variant the processes of aggregation and oxidative stress, causing the inflammation and neuronal damage are related to the formation of reactive Cu(II) complexes with Aβ peptides. Aβ peptides are a family of molecules with similar amino acid sequences, differing mainly by the presence of longer or shorter terminal sequences. Their physiological role of is unclear. Aβ1-42 and Aβ1-40 have been mostly studied, but most studies have ignored a very abundant N-terminally truncated species Aβ4-42. We recognized it, and more gene-rally the Aβ4-x peptide family as potentially strong Cu(II) ligands, due to the presence at their N-termini of the Phe-Arg-His amino acid sequence, comprising the ATCUN/NTS structural motif. This observation was followed by vigorous research performed in our laboratory. We studied the ability of Aβ4-x peptides to bind Cu(II) ions, their electrochemical properties and redox reactivity, interactions with proteins which bind copper under physiological conditions, their aggregation properties in the Cu(II) presence and susceptibility to proteolysis. Additionally, we investigated their interaction with a molecule of a therapeutic potential. We demonstrated that Aβ4-x peptides can be primary copper bin-ding agents in extracellular spaces in the brain, able to instantaneously intercept copper from Aβ1-x peptides studied so far. Cu(II) complexes of Aβ4-x peptides are highly resistant to oxidation and reduction, release copper ions to other molecules slowly and reluctantly, and do not produce reactive oxygen species. In accordance with these properties we proposed a physiological role for the Aβ4-42 peptide as a molecule cleansing the synaptic cleft from Cu2+ ions and thereby assuring the correct neurotransmission. This function can however be disturbed by an inappropriate pharmacological intervention. The results of studies of the effect of cupric ions on the aggregation and membrane interactions of the Aβ4-40 peptides suggest that copper can inhibit the Aβ4-x peptides toxicity, thereby providing an additional support for our concept. Studies of hydrolysis of Aβ peptides and properties of its products revealed a possibility for a significant role of short fragments in the brain copper physiology. Our hypothesis awaits verification by biological studies. The issue of metabolism of the studied complexes is a key issue remaining to be solved.
    Źródło:
    Wiadomości Chemiczne; 2019, 73, 5-6; 351-366
    0043-5104
    2300-0295
    Pojawia się w:
    Wiadomości Chemiczne
    Dostawca treści:
    Biblioteka Nauki
    Artykuł
    Tytuł:
    Alzheimers disease: Its origin at the membrane, evidence and questions.
    Autorzy:
    Buchet, Rene
    Pikuła, Sławomir
    Powiązania:
    https://bibliotekanauki.pl/articles/1044315.pdf
    Data publikacji:
    2000
    Wydawca:
    Polskie Towarzystwo Biochemiczne
    Tematy:
    β-amyloid precursor protein
    membrane proteases
    Alzheimer's disease
    lipid composition
    membrane microdomains
    Opis:
    Numerous results on membrane lipid composition from different regions of autopsied Alzheimer's disease brains in comparison with corresponding fractions isolated from control brains revealed significant differences in serine- and ethanolamine-containing glycerophospholipid as well as in glycosphingolipid content. Changes in membrane lipid composition are frequently accompanied by alterations in membrane fluidity, hydrophobic mismatch, lipid signaling pathways, transient formation and disappearance of lipid microdomains, changes in membrane permeability to cations and variations of other membrane properties. In this review we focus on possible implications of altered membrane composition on β-amyloid precursor protein (APP) and on proteolysis of APP leading eventually to the formation of neurotoxic β-amyloid (Aβ) peptides, the major proteinaceous component of extracellular senile plaques, directly involved in Alzheimer's disease pathogenesis.
    Źródło:
    Acta Biochimica Polonica; 2000, 47, 3; 725-733
    0001-527X
    Pojawia się w:
    Acta Biochimica Polonica
    Dostawca treści:
    Biblioteka Nauki
    Artykuł
    Tytuł:
    Circular dichroism and aggregation studies of amyloid β (11-8) fragment and its variants.
    Autorzy:
    Juszczyk, Paulina
    Kołodziejczyk, Aleksandra
    Grzonka, Zbigniew
    Powiązania:
    https://bibliotekanauki.pl/articles/1041423.pdf
    Data publikacji:
    2005
    Wydawca:
    Polskie Towarzystwo Biochemiczne
    Tematy:
    secondary structure studies
    thioflavine T assay
    aggregation studies.
    Alzheimer's disease
    amyloid β
    circular dichroism (CD)
    Opis:
    Aggregation of Aβ peptides is a seminal event in Alzheimer's disease. Detailed understanding of Aβ assembly would facilitate the targeting and design of fibrillogenesis inhibitors. Here comparative conformational and aggregation studies using CD spectroscopy and thioflavine T fluorescence assay are presented. As a model peptide, the 11-28 fragment of Aβ was used. This model peptide is known to contain the core region responsible for Aβ aggregation. The structural and aggregational behaviour of the peptide was compared with the properties of its variants corresponding to natural, clinically relevant mutants at positions 21-23 (A21G, E22K, E22G, E22Q and D23N). In HFIP (hexafluoro-2-propanol), a strong α-helix inducer, the CD spectra revealed an unexpectedly high amount of β-sheet conformation. The aggregation process of Aβ(11-28) variants provoked by water addition to HFIP was found to be consistent with a model of an α-helix-containing intermediate. The aggregation propensity of all Aβ(11-28) variants was also compared and discussed.
    Źródło:
    Acta Biochimica Polonica; 2005, 52, 2; 425-431
    0001-527X
    Pojawia się w:
    Acta Biochimica Polonica
    Dostawca treści:
    Biblioteka Nauki
    Artykuł
    Tytuł:
    Molecular mechanisms initiating amyloid β-fibril formation in Alzheimers disease
    Autorzy:
    Kirkitadze, Marina
    Kowalska, Anna
    Powiązania:
    https://bibliotekanauki.pl/articles/1041422.pdf
    Data publikacji:
    2005
    Wydawca:
    Polskie Towarzystwo Biochemiczne
    Tematy:
    protein aggregation
    fibrillogenesis
    Alzheimer's disease
    neurotoxicity
    amyloid-β
    APP mutations
    Opis:
    The deposition of aggregated amyloid β-protein (Aβ) in the human brain is a major lesion in Alzheimer' disease (AD). The process of Aβ fibril formation is associated with a cascade of neuropathogenic events that induces brain neurodegeneration leading to the cognitive and behavioral decline characteristic of AD. Although a detailed knowledge of Aβ assembly is crucial for the development of new therapeutic approaches, our understanding of the molecular mechanisms underlying the initiation of Aβ fibril formation remains very incomplete. The genetic defects responsible for familial AD influence fibrillogenesis. In a majority of familial cases determined by amyloid precursor protein (APP) and presenilin (PS) mutations, a significant overproduction of Aβ and an increase in the Aβ42/Aβ40 ratio are observed. Recently, it was shown that the two main alloforms of Aβ have distinct biological activity and behaviour at the earliest stage of assembly. In vitro studies demonstrated that Aβ42 monomers, but not Aβ40, form initial and minimal structures (pentamer/hexamer units called paranuclei) that can oligomerize to larger forms. It is now apparent that Aβ oligomers and protofibrils are more neurotoxic than mature Aβ fibrils or amyloid plaques. The neurotoxicity of the prefibrillar aggregates appears to result from their ability to impair fundamental cellular processes by interacting with the cellular membrane, causing oxidative stress and increasing free Ca^(2+)that eventually lead to apoptotic cell death.
    Źródło:
    Acta Biochimica Polonica; 2005, 52, 2; 417-423
    0001-527X
    Pojawia się w:
    Acta Biochimica Polonica
    Dostawca treści:
    Biblioteka Nauki
    Artykuł
    Tytuł:
    Targeting BACE with small inhibitory nucleic acids - a future for Alzheimers disease therapy?
    Autorzy:
    Nawrot, Barbara
    Powiązania:
    https://bibliotekanauki.pl/articles/1043280.pdf
    Data publikacji:
    2004
    Wydawca:
    Polskie Towarzystwo Biochemiczne
    Tematy:
    β-amyloid peptide
    deoxyribozymes
    small interfering RNAs
    hammerhead ribozymes
    Alzheimer's disease
    β-secretase
    Opis:
    β-Secretase, a β-site amyloid precursor protein (APP) cleaving enzyme (BACE), participates in the secretion of β-amyloid peptides (Aβ), the major components of the toxic amyloid plaques found in the brains of patients with Alzheimer's disease (AD). According to the amyloid hypothesis, accumulation of Aβ is the primary influence driving AD pathogenesis. Lowering of Aβ secretion can be achieved by decreasing BACE activity rather than by down-regulation of the APP substrate protein. Therefore, β-secretase is a primary target for anti-amyloid therapeutic drug design. Several approaches have been undertaken to find an effective inhibitor of human β-secretase activity, mostly in the field of peptidomimetic, non-cleavable substrate analogues. This review describes strategies targeting BACE mRNA recognition and its down-regulation based on the antisense action of small inhibitory nucleic acids (siNAs). These include antisense oligonucleotides, catalytic nucleic acids - ribozymes and deoxyribozymes - as well as small interfering RNAs (siRNAs). While antisense oligonucleotides were first used to identify an aspartyl protease with β-secretase activity, all the strategies now demonstrate that siNAs are able to inhibit BACE gene expression in a sequence-specific manner, measured both at the level of its mRNA and at the level of protein. Moreover, knock-down of BACE reduces the intra- and extracellular population of Aβ40 and Aβ42 peptides. An anti-amyloid effect of siNAs is observed in a wide spectrum of cell lines as well as in primary cortical neurons. Thus targeting BACE with small inhibitory nucleic acids may be beneficial for the treatment of Alzheimer's disease and for future drug design.
    Źródło:
    Acta Biochimica Polonica; 2004, 51, 2; 431-444
    0001-527X
    Pojawia się w:
    Acta Biochimica Polonica
    Dostawca treści:
    Biblioteka Nauki
    Artykuł
    Tytuł:
    The role of the Amyloid Precursor Protein mutations and PERKdependent signaling pathways in the pathogenesis of Alzheimer’s disease
    Autorzy:
    Rozpędek, Wioletta
    Nowak, Alicja
    Pytel, Dariusz
    Lewko, Dawid
    Diehl, J. Alan
    Majsterek, Ireneusz
    Powiązania:
    https://bibliotekanauki.pl/articles/764808.pdf
    Data publikacji:
    2016
    Wydawca:
    Uniwersytet Łódzki. Wydawnictwo Uniwersytetu Łódzkiego
    Tematy:
    Amyloid β
    Endoplasmic Reticulum stress
    Unfolded Protein Response
    eIF2α
    CHOP
    Opis:
    Choroba Alzheimera (ang. Alzheimer’s disease, AD) jest przewlekłą, najczęściej występującą, chorobą neurodegeneracyjną prowadzącą do nieodwracalnych zmian w strukturze, biochemii i funkcjach mózgu. Neurodegeneracja Ośrodkowego Układu Nerwowego (OUN) jest wynikiem odkładania toksycznych złogów amyloidu β (Aβ) w tkance nerwowej mózgu. Rozwój AD jest przyczyną skomplikowanych interakcji między podłożem genetycznym, a czynnikami biologicznymi, które aktywują złożone szlaki molekularne w przebiegu schorzenia. Za jedną z głównych przyczyn uważa się mutacje występujące w genie kodującym Prekursorowe białko amyloidu β (ang. Amyloid beta Precursor Protein, APP) zlokalizowane w pobliżu cięcia białka APP przez wysoce specyficzne sekretazy: α, β oraz γ. Generowanie toksycznej formy Aβ o długości 42-óch aminokwasów, odkładanego w tkance mózgowej jako płytki starcze, zachodzi poprzez drogę amyloidogenną, w której uczestniczą sekretazy β oraz γ. Na podłożu molekularnym główną przyczyną rozwoju choroby AD jest akumulacja błędnie sfałdowanych lub niesfałdowanych białek w lumen Retikulum Plazmatycznego (ang. Endoplasmic Reticulum, ER). Skutkuje to bezpośrednim wywołaniem stresu ER, który prowadzi do aktywacji kinazy PERK, a następnie fosforylacji eukariotycznego czynnika inicjacji translacji 2 (eIF2α). W rezultacie w komórce nerwowej inhibowana jest translacja większości białek oraz dochodzi do preferencyjnej translacji wyłącznie takich białek takich jak ATF4 (ang. Activating Transcriptor 4) oraz, wyniku długotrwałych warunków stresowych, CHOP (ang. CCAAT-enhancer-binding protein homologous protein). Nadekspresja białka CHOP prowadzi do wzmocnienia ekspresji genów kodujących: pro-apoptotyczne białka BH3 domain-only, GADD34 (ang. DNA damage-inducible protein, GADD34 oraz białko o aktywności oksydoreduktazy ER (ang. ER oxidoreductin 1α, ERO1α). W warunkach wysokiego stężenia białka CHOP zostaje osłabiona ekspresja genów kodujących anty-apoptotyczne białka Bcl-2. W rezultacie masa tkanki nerwowej mózgu ulega znaczącemu obniżeniu w wyniku postępującego procesu neurodegeneracji na drodze apoptotycznej śmierć komórkowej w przebiegu AD.
    Alzheimer’s disease (AD) is a highly complex, progressive, age-related neurodegenerative human disease entity. The genetic basis of AD is strictly connected with occurrence of mutations in Amyloid Precursor (APP) gene on chromosome 21. Molecular mechanism that leads to AD development still remains unclear. Recent data reported that it is closely correlated with Endoplasmic Reticulum (ER) stress conditions, which subsequently activate Unfolded Protein Response (UPR) signaling pathways, via the induction of protein kinase RNA-like endoplasmic reticulum kinase (PERK), as a self-protective, adaptive response to adverse stress conditions. That results in the attenuation of global protein synthesis and, on the contrary, selective translation of Activating Transcriptor Factor 4 (ATF4) and secretase β. Interestingly, under prolonged, severe ER stress UPR may switch its signal into apoptotic cell death. That ensues by ATF4-CHOP-mediated activation of a range of pro-apoptotic genes and, on the other hand, downregulation of the expression of the anti-apoptotic protein B-cell lymphoma 2 (Bcl-2) genes. Current investigations suggest that inhibitions of PERK activity may contribute to the attenuation of the deposition of toxic senile plaques in the brain tissue and, as a result, prevent degeneration of neurons and decline in cognitive abilities.
    Źródło:
    Acta Universitatis Lodziensis. Folia Biologica et Oecologica; 2016, 12; 48-59
    1730-2366
    2083-8484
    Pojawia się w:
    Acta Universitatis Lodziensis. Folia Biologica et Oecologica
    Dostawca treści:
    Biblioteka Nauki
    Artykuł
    Tytuł:
    Chromatin acetylation, β-amyloid precursor protein and its binding partner FE65 in DNA double strand break repair
    Autorzy:
    Szumiel, Irena
    Foray, Nicolas
    Powiązania:
    https://bibliotekanauki.pl/articles/1039940.pdf
    Data publikacji:
    2011
    Wydawca:
    Polskie Towarzystwo Biochemiczne
    Tematy:
    chromatin acetylation
    FE65
    MOF acetyltransferase
    DNA double strand break repair
    β-amyloid precursor protein
    Tip60 histone acetyltransferase
    heterochromatin protein 1
    Opis:
    Among post-translational modifications of chromatin proteins taking place in DNA double strand break (DSB) repair, acetylation plays a prominent role. This review lists several facts and hypotheses concerning this process. Lack of acetyltransferase TIP60 (HIV-Tat interacting protein of 60 kDa) activity results in cells with defective DSB repair. The enzyme is present in the nucleus in a multimeric protein complex. TIP60 dependent activation of ATM (ataxia telangiectasia mutated kinase) is an early event in the response to DNA breakage. Other important acetylations are those of histones H4 and γH2AX. Correct reconstruction of the damaged site is critical for survival and prevention of genetic and epigenetic changes in the cell that may affect the function of its daughter cells. Recently, two proteins with previously unsuspected functions in DSB repair have been identified as active in this process: Alzheimer β-amyloid precursor protein (APP) and its binding partner FE65, β-amyloid precursor binding protein. Their participation in DSB repair in both neuronal and non-neuronal cells is related to acetylation carried out by the acetyltransferase complex. The same function is ascribed to heterochromatin protein 1 (HP1). So far, the relations (if any) between TIP60 activation by HP1 and by the FE65 complex remain unidentified.
    Źródło:
    Acta Biochimica Polonica; 2011, 58, 1; 11-18
    0001-527X
    Pojawia się w:
    Acta Biochimica Polonica
    Dostawca treści:
    Biblioteka Nauki
    Artykuł
    Tytuł:
    Rola metali w rozwoju choroby Alzheimera i Parkinsona
    The role of metals in development Alzheimer's and Parkinson's diseases
    Autorzy:
    Żygowska, Justyna
    Szymańska, Aneta
    Powiązania:
    https://bibliotekanauki.pl/articles/2057913.pdf
    Data publikacji:
    2022
    Wydawca:
    Polskie Towarzystwo Chemiczne
    Tematy:
    choroba neurodegeneracyjna
    jony metali
    β-amyloid
    białka amyloidogenne
    choroba Alzheimera
    choroba Parkinsona
    neurodegenerative diseases
    amyloidogenic proteins
    amyloid β
    metal ions
    Alzheimer's disease
    Parkinson disease
    Opis:
    Neurodegenerative diseases are the consequence of progressive brain degeneration caused by the death of nerve cells. Many factors that influence the neurodegeneration development are still not fully known. A lot of studies indicate the contribution of metal ions in this process. Copper, zinc, and iron are trace elements essential for proper functioning of the body. They are part of many enzymes participating in the transmission of the nerve signals, electrons transport, neurotransmitters and nucleic acids synthesis, and oxygen storage. Disorder of metals homeostasis leads to the development of severe diseases and nervous system degenerations. An excess of copper and iron ions causes a significant increase in cellular oxidative stress. Metals catalyze the reactions of free radicals formation that destroy proteins, lipids, and nucleic acids. High concentration of copper and iron ions were found in the deposits of amyloidogenic proteins. Amyloid β (Alzheimer disease) and α synuclein (Parkinson disease) have ions binding chain structures. The metal-protein interaction increases oligomerization speed in vitro. A lot of evidence suggests that the disorder of Cu, Zn and Fe homeostasis accelerates the progress of brain neurodegeneration. Human organism contains many metals, which are not needed for the proper functioning of the body, e.g. aluminum. Al binds to nucleic acids causing an increase in cellular oxidative stress and initiating proteins oligomerization. The presence of aluminum is also considered to be disadvantageous for the nervous system. The lack of medicines for neurodegenerative diseases forces us to search for new therapies. The development of degenerations could be slowed down by chelators of toxic metals, but first, these diseases must be better understood. Adverse effects of high concentration of metal ions on brain functioning are not fully known. This knowledge is necessary to find effective drugs.
    Źródło:
    Wiadomości Chemiczne; 2022, 76, 1-2; 1-25
    0043-5104
    2300-0295
    Pojawia się w:
    Wiadomości Chemiczne
    Dostawca treści:
    Biblioteka Nauki
    Artykuł
      Wyświetlanie 1-9 z 9

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