How the CORAL software can be used to select compounds for efficient treatment of neurodegenerative diseases?

2020 ◽  
Vol 408 ◽  
pp. 115276
Author(s):  
Alla P. Toropova ◽  
Andrey A. Toropov ◽  
Danuta Leszczynska ◽  
Jerzy Leszczynski
2013 ◽  
Vol 55 ◽  
pp. 119-131 ◽  
Author(s):  
Bernadette Carroll ◽  
Graeme Hewitt ◽  
Viktor I. Korolchuk

Autophagy is a process of lysosome-dependent intracellular degradation that participates in the liberation of resources including amino acids and energy to maintain homoeostasis. Autophagy is particularly important in stress conditions such as nutrient starvation and any perturbation in the ability of the cell to activate or regulate autophagy can lead to cellular dysfunction and disease. An area of intense research interest is the role and indeed the fate of autophagy during cellular and organismal ageing. Age-related disorders are associated with increased cellular stress and assault including DNA damage, reduced energy availability, protein aggregation and accumulation of damaged organelles. A reduction in autophagy activity has been observed in a number of ageing models and its up-regulation via pharmacological and genetic methods can alleviate age-related pathologies. In particular, autophagy induction can enhance clearance of toxic intracellular waste associated with neurodegenerative diseases and has been comprehensively demonstrated to improve lifespan in yeast, worms, flies, rodents and primates. The situation, however, has been complicated by the identification that autophagy up-regulation can also occur during ageing. Indeed, in certain situations, reduced autophagosome induction may actually provide benefits to ageing cells. Future studies will undoubtedly improve our understanding of exactly how the multiple signals that are integrated to control appropriate autophagy activity change during ageing, what affect this has on autophagy and to what extent autophagy contributes to age-associated pathologies. Identification of mechanisms that influence a healthy lifespan is of economic, medical and social importance in our ‘ageing’ world.


2020 ◽  
Vol 4 (6) ◽  
pp. 645-675
Author(s):  
Parasuraman Padmanabhan ◽  
Mathangi Palanivel ◽  
Ajay Kumar ◽  
Domokos Máthé ◽  
George K. Radda ◽  
...  

Neurodegenerative diseases (NDDs), including Alzheimer's disease (AD) and Parkinson's disease (PD), affect the ageing population worldwide and while severely impairing the quality of life of millions, they also cause a massive economic burden to countries with progressively ageing populations. Parallel with the search for biomarkers for early detection and prediction, the pursuit for therapeutic approaches has become growingly intensive in recent years. Various prospective therapeutic approaches have been explored with an emphasis on early prevention and protection, including, but not limited to, gene therapy, stem cell therapy, immunotherapy and radiotherapy. Many pharmacological interventions have proved to be promising novel avenues, but successful applications are often hampered by the poor delivery of the therapeutics across the blood-brain-barrier (BBB). To overcome this challenge, nanoparticle (NP)-mediated drug delivery has been considered as a promising option, as NP-based drug delivery systems can be functionalized to target specific cell surface receptors and to achieve controlled and long-term release of therapeutics to the target tissue. The usefulness of NPs for loading and delivering of drugs has been extensively studied in the context of NDDs, and their biological efficacy has been demonstrated in numerous preclinical animal models. Efforts have also been made towards the development of NPs which can be used for targeting the BBB and various cell types in the brain. The main focus of this review is to briefly discuss the advantages of functionalized NPs as promising theranostic agents for the diagnosis and therapy of NDDs. We also summarize the results of diverse studies that specifically investigated the usage of different NPs for the treatment of NDDs, with a specific emphasis on AD and PD, and the associated pathophysiological changes. Finally, we offer perspectives on the existing challenges of using NPs as theranostic agents and possible futuristic approaches to improve them.


VASA ◽  
2016 ◽  
Vol 45 (1) ◽  
pp. 49-56 ◽  
Author(s):  
Frantisek Stanek ◽  
Radoslava Ouhrabkova ◽  
David Prochazka

Abstract. Background: The aim of this prospective single-centre study was to analyse the immediate results, failures and complications of percutaneous mechanical thrombectomy using the Rotarex catheter in the treatment of acute and subacute occlusions of peripheral arteries and bypasses, as well as to evaluate long-term outcomes of this method. Patients and methods: Patients with acute (duration of symptoms < 14 days) or subacute (duration of symptoms > 14 days and < 3 months) occlusions of peripheral arteries and bypasses were selected consecutively for treatment. The cohort consisted of 113 patients, aged 18 - 92 years (median 72 years). In all, 128 procedures were performed. Results: Angiographic success was obtained in 120 interventions (93.8 %). Reasons for failures were rethrombosis of a partially recanalised segment in six procedures, and embolism into crural arteries in one intervention - percutaneous aspiration thromboembolectomy (PAT) and/or thrombolysis were ineffective in all these cases. Breakage of the Rotarex catheter happened in one procedure. Embolisation into crural arteries as a transitory complication solvable with PAT and/or thrombolysis occurred in four cases. Rethrombosis was more frequent in bypasses than in native arteries (p = 0.0069), in patients with longer occlusions (p = 0.026) and those with poorer distal runoff (p = 0.048). Embolisation happened more often in patients with a shorter duration of symptoms (p = 0.0001). Clinical success was achieved in 82.5 %. Major amputation was performed in 10 % of cases. Cumulative patency rates were 75 % after one month, 71 % after six months, 38 % after 12 months, 33 % after 18 months and 30 % after 24, 30, 36 and 42 months. Conclusions: Rotarex thrombectomy has excellent immediate results with a low rate of failures and complications. In comparison to thrombolysis, it enables the fast and efficient treatment of acute and subacute occlusions of peripheral arteries in one session.


2008 ◽  
Vol 35 (S 01) ◽  
Author(s):  
T Frank ◽  
K Meuer ◽  
C Pitzer ◽  
J Schulz ◽  
M Bähr ◽  
...  

2013 ◽  
Vol 46 (06) ◽  
Author(s):  
I Denzer ◽  
M Pischetsrieder ◽  
K Leuner

INEOS OPEN ◽  
2020 ◽  
Vol 3 ◽  
Author(s):  
S. A. Sorokina ◽  
◽  
Yu. Yu. Stroilova ◽  
V. I. Muronets ◽  
Z. B. Shifrina ◽  
...  

Among the compounds able to efficiently inhibit the amyloid aggregation of proteins and decompose the amyloid aggregates that cause neurodegenerative diseases, of particular interest are dendrimers, which represent individual macromolecules with the hypercrosslinked architectures and given molecular parameters. This short review outlines the peculiarities of the antiamyloid activity of dendrimers and discusses the effect of dendrimer structures and external factors on their antiamyloid properties. The potential of application of dendrimers in further investigations on the aggregation processes of amyloid proteins as the compounds that exhibit the remarkable antiamyloid activity is evaluated.


2000 ◽  
Vol 653 ◽  
Author(s):  
Celeste Sagui ◽  
Thoma Darden

AbstractFixed and induced point dipoles have been implemented in the Ewald and Particle-Mesh Ewald (PME) formalisms. During molecular dynamics (MD) the induced dipoles can be propagated along with the atomic positions either by interation to self-consistency at each time step, or by a Car-Parrinello (CP) technique using an extended Lagrangian formalism. The use of PME for electrostatics of fixed charges and induced dipoles together with a CP treatment of dipole propagation in MD simulations leads to a cost overhead of only 33% above that of MD simulations using standard PME with fixed charges, allowing the study of polarizability in largemacromolecular systems.


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