The monomers, oligomers, and fibrils of amyloid-β inhibit the activity of mitoBKCa channels by a membrane-mediated mechanism

Kravenskaya, E. V.; Nieznanska, Hanna; Nieznañski, Krzysztof; Lukyanetz, E. A.; Szewczyk, Adam; Koprowski, Piotr

doi:10.1016/j.bbamem.2020.183337

Cited by 34 publications

(28 citation statements)

References 118 publications

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“…Our previous researches have addressed some aspects of this problem. In our previous experiments, we have shown that mitochondria , K + ion channels of mitochondria are subject to changes in AD modeling [18,19]. The role of calcium ions also has been shown [20,21].…”

Section: Discussionmentioning

confidence: 96%

Effect of avandamet on conditioned food reflex in rats of different age groups

Gorbachenko¹,

Kruchenko²,

Lukyanetz³

2020

Fiziol Zh

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The prevalence of Alzheimer’s disease (AD) is increasing in the absence of truly effective treatments. The recently discovered causal link between AD and type 2 diabetes mellitus (T2DM) (non-insulin-dependent diabetes mellitus) suggests that an increase in insulin receptor resistance may affect brain aging and lead to AD. In our experiments, we tested Avandamet (AVD), the antidiabetic drug used for the treatment of T2DM, on temporary parameters of conditioning food reflex in rats. We measured the individual components of the sensorimotor reaction (SMR) of rats, which reflect CNS’s functional state. Important tha7t rosiglitazone is the main component of AVD. It acts by activating the nuclear peroxisome proliferator-activated receptor (PPAR) gamma. Our data showed that this drug influences the brain function of both young and old rats. It is proved that AVD affects the CNS of rats by increasing their excitability. Considering the obtained data from the point of view of AD, the time parameter, which changed more significantly in old rats, was responsible for analyzing the situation and speed of action. Under AVD’s influence, old rats became more agile and had increased motor activity, also the success of rats in performing a conditioned reflex was increased. Thus, the drug AVD and its active component rosiglitazone can be perspective for its testing in AD treatment.

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Section: Discussionmentioning

confidence: 96%

Effect of avandamet on conditioned food reflex in rats of different age groups

Gorbachenko¹,

Kruchenko²,

Lukyanetz³

2020

Fiziol Zh

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“…Нині існує декілька теорій механізму виникнення ХА, серед яких ацетилхолінова, мітохондріальна, кальцієва, метаболічна та інші. І дійсно, у низці наших праць показано вплив Aβ на функцію мітохондрій [27][28][29], кальцієві канали, мембрани нейронів і кальцієвий гомеостаз. Численні дані свідчать про те, що ХА може виникати внаслідок порушень в убіквітин-протеасомній системі, яка відіграє важливу роль у регулюванні багатьох клітинних функцій [29].…”

Section: молекулярні механізми нейродегенератив них процесів при хворunclassified

The Role of Beta-Amyloid in Norm and at Alzheimer`s Disease

Tyshchenko¹,

Lukyanetz²

2020

Fiziol Zh

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Alzheimer’s disease (AD) is a neurodegenerative disease characterized by progressive cognitive impairment and memory loss. The pathogenesis of AD is complex, depends on many factors, and has not yet been fully studied. Extracellular deposits of amyloid-beta (Ab) peptide in the form of senile plaques, the formation of intracellular neurofibrillary tangles, and massive neuronal loss are considered as the main pathological signs of AD. However, recently there have been many data that indicate other pathways involved in the pathogenesis of AD. This review aims to analyze the existing data on the physiological role of Ab in the brain under normal conditions and its pathological role in Alzheimer’s disease.

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“…Novel mechanisms of regulation of mitoBK Ca channels such as amyloid-β (Aβ) are also emerging. Aβ is a peptide that accumulates in brain in Alzheimer´s Disease and inhibits the activity of mitoBK Ca channels [ 5 ]. Confirmation of this effect by other laboratories might have important implications in our understanding of AD and possibly on the development of new treatments for neurodegenerative diseases.…”

Section: Introductionmentioning

confidence: 99%

“…Interestingly, a recent study on mitoplasts from human astrocytoma cells has reported that different forms of Aβ, including monomers, oligomers and fibrils inhibit the activity of mitoBK Ca channels in a concentration dependent manner. The highest concentration of Aβ fibrils tested (5 µM) produced an 80% inhibition, whereas Aβ monomers and oligomers inhibited 50% and 70% of mitoBK Ca channel activity, respectively [ 5 ]. All forms of Aβ inhibited mitoBK Ca channel activity when applied at either side of the membrane [ 5 ], indicative of an indirect effect on the channel.…”

Section: Introductionmentioning

confidence: 99%

Regulatory mechanisms of mitochondrial BK_Ca channels

et al. 2021

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The mitochondrial BK Ca channel (mitoBK Ca ) is a splice variant of plasma membrane BK Ca (Maxi-K, BK Ca , Slo1, K Ca 1.1). While a high-resolution structure of mitoBK Ca is not available yet, functional and structural studies of the plasma membrane BK Ca have provided important clues on the gating of the channel by voltage and Ca 2+ , as well as the interaction with auxiliary subunits. To date, we know that the control of expression of mitoBK Ca , targeting and voltage-sensitivity strongly depends on its association with its regulatory β1-subunit, which overall participate in the control of mitochondrial Ca 2+ -overload in cardiac myocytes. Moreover, novel regulatory mechanisms of mitoBK Ca such as β-subunits and amyloid-β have recently been proposed. However, major basic questions including how the regulatory BK Ca -β1-subunit reaches mitochondria and the mechanism through which amyloid-β impairs mitoBK Ca channel function remain to be addressed.

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The monomers, oligomers, and fibrils of amyloid-β inhibit the activity of mitoBKCa channels by a membrane-mediated mechanism

Cited by 34 publications

References 118 publications

Effect of avandamet on conditioned food reflex in rats of different age groups

Effect of avandamet on conditioned food reflex in rats of different age groups

The Role of Beta-Amyloid in Norm and at Alzheimer`s Disease

Regulatory mechanisms of mitochondrial BK_Ca channels

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The monomers, oligomers, and fibrils of amyloid-β inhibit the activity of mitoBKCa channels by a membrane-mediated mechanism

Cited by 34 publications

References 118 publications

Effect of avandamet on conditioned food reflex in rats of different age groups

Effect of avandamet on conditioned food reflex in rats of different age groups

The Role of Beta-Amyloid in Norm and at Alzheimer`s Disease

Regulatory mechanisms of mitochondrial BKCa channels

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Regulatory mechanisms of mitochondrial BK_Ca channels