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1.
Biochemistry (Mosc) ; 83(9): 1068-1074, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30472945

RESUMO

Alzheimer's disease (AD) is the most common incurable neurodegenerative disorder that affects the processes of memory formation and storage. The loss of dendritic spines and alteration in their morphology in AD correlate with the extent of patient's cognitive decline. Tubulin had been believed to be restricted to dendritic shafts, until recent studies demonstrated that dynamically growing tubulin microtubules enter dendritic spines and promote their maturation. Abnormalities of tubulin cytoskeleton may contribute to the process of dendritic spine shape alteration and their subsequent loss in AD. In this review, association between tubulin cytoskeleton dynamics and dendritic spine morphology is discussed in the context of dendritic spine alterations in AD. Potential implications of these findings for the development of AD therapy are proposed.


Assuntos
Doença de Alzheimer/patologia , Espinhas Dendríticas/metabolismo , Microtúbulos/metabolismo , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Citoesqueleto/efeitos dos fármacos , Citoesqueleto/metabolismo , Espinhas Dendríticas/patologia , Epotilonas/química , Epotilonas/metabolismo , Epotilonas/uso terapêutico , Humanos , Neurônios/metabolismo , Nocodazol/química , Nocodazol/metabolismo , Nocodazol/uso terapêutico
2.
Bull Exp Biol Med ; 164(2): 252-258, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29177899

RESUMO

Huntington's disease is a hereditary neurodegenerative disease that primarily affects striatal neurons. Recent studies demonstrated abnormalities in calcium regulation in striatal neurons in Huntington's disease, which leads to elimination of synaptic connections between cortical and striatal neurons. In the present study, we focused on the neuroprotective properties of σ1-receptor, because one of its main functions is associated with modulation of calcium homeostasis in cells. The application of selective σ1-receptor agonists to the corticostriatal cell culture restores synaptic connections between the cortical and striatal neurons. Based on the obtained data, we assume that σ1-receptor is a promising target for the development of drugs for the therapy of Huntington's disease.


Assuntos
Cálcio/metabolismo , Doença de Huntington/genética , Neurônios/metabolismo , Receptores sigma/genética , Transmissão Sináptica/genética , Animais , Anisóis/farmacologia , Córtex Cerebral/metabolismo , Córtex Cerebral/patologia , Corpo Estriado/metabolismo , Espinhas Dendríticas/metabolismo , Espinhas Dendríticas/patologia , Expressão Gênica , Homeostase , Doença de Huntington/metabolismo , Doença de Huntington/patologia , Masculino , Camundongos , Modelos Biológicos , Morfolinas/farmacologia , Neurônios/patologia , Piperidinas/farmacologia , Cultura Primária de Células , Propilaminas/farmacologia , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Receptores sigma/agonistas , Receptores sigma/antagonistas & inibidores , Receptores sigma/metabolismo , Sinapses/metabolismo , Sinapses/patologia , Transdução Genética , Receptor Sigma-1
5.
Acta Naturae ; 2(1): 72-82, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22649630

RESUMO

Neurodegenerative disorders, such as Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), and spinocerebellar ataxias (SCA) are very important both for fundamental science and for practical medicine. Despite extensive research into the causes of these diseases, clinical researchers have had very limited progress and, as of now, there is still no cure for any of these diseases. One of the main obstacles in the way of creating treatments for these disorders is the fact that their etiology and pathophysiology still remain unclear. This paper reviews results that support the so-called "calcium hypothesis of neurodegenerative diseases." The calcium hypothesis states that the atrophic and degenerative processes in the neurons of AD, PD, ALS, HD, and SCA patients are accompanied by alterations in calcium homeostasis. Moreover, the calcium hypothesis states that this deregulation of calcium signaling is one of the early-stage and key processes in the pathogenesis of these diseases. Based on the results we reviewed, we conclude that the calcium channels and other proteins involved in the neuronal calcium signaling system are potential drug targets for AD, PD, ALS, HD, and SCA therapy.

6.
Acta Naturae ; 2(3): 94-100, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22649656

RESUMO

Store-operated channels are major calcium influx pathways in nonexitable cells. Homer scaffold proteins are well known for their role in regulating calcium signaling. Here we report on a detailed single-channel level characterization of native store-operated channels regulated by Homer scaffold proteins in A431 carcinoma cells. By applying the single-channel patch-clamp technique, we found that different types of store-operated calcium channels have different sensitivities to Homer proteins.

7.
Mol Biol Cell ; 4(3): 347-52, 1993 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-7683508

RESUMO

Heparin has been used as a potent competitive inhibitor of inositol 1,4,5-trisphosphate (IP3)-binding to IP3 receptors and to block IP3-gated calcium channels in bilayer experiments. In contrast to the effect on the IP3-gated channel, heparin (0.1-1 micrograms/ml) opened the Ca release channel (ryanodine receptor). Other polyanions such as pentosan polysulfate and polyvinyl sulfate also activated the Ca release channel. The effect of polyanions on the Ca release channel was Ca dependent. Polyanion addition activated the Ca release channel when free Ca was > 80 nM, but was ineffective when free Ca was < 20 nM. The level of channel activation could be altered by manipulating the free Ca concentration. These results suggest that the polyanions act by increasing the local concentration of Ca near regulatory sites on the channel complex. As most cells have both types of intracellular channels, the opposite effects of the polyanions on the two channel types suggests that addition of polyanions to intact cells may produce multiple effects.


Assuntos
Canais de Cálcio/efeitos dos fármacos , Cálcio/metabolismo , Heparina/farmacologia , Proteínas Musculares/efeitos dos fármacos , Animais , Canais de Cálcio/metabolismo , Técnicas In Vitro , Inositol 1,4,5-Trifosfato/metabolismo , Ativação do Canal Iônico , Proteínas Musculares/metabolismo , Poliéster Sulfúrico de Pentosana/farmacologia , Coelhos , Canal de Liberação de Cálcio do Receptor de Rianodina , Retículo Sarcoplasmático/efeitos dos fármacos , Retículo Sarcoplasmático/metabolismo
8.
Biochim Biophys Acta ; 1064(1): 75-80, 1991 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-2025637

RESUMO

The activity of potassium channels of canine aortic sarcoplasmic reticulum was measured using the planar lipid bilayer-fusion technique. The channels have a conductance of 208 pS (400/100 mM K+ in cis/trans solutions) and potassium-to-sodium permeability ratio of 7.7 Ba2+ ions produced two main effects: one is the interruption of channel currents for tens to hundreds of milliseconds in a voltage-dependent manner, and the other is the appearance of a second conductance level with amplitude about 60% of the main level.


Assuntos
Músculo Liso Vascular/química , Canais de Potássio/química , Retículo Sarcoplasmático/química , Animais , Aorta , Bário , Cátions , Cães , Condutividade Elétrica , Microssomos/química , Potássio , Sódio
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