Fullerene-Derivatives as Therapeutic Agents in Respiratory System and Neurodegenerative Disorders

2015 ◽  
pp. 71-84 ◽  
Author(s):  
Virginia Soares Lemos ◽  
Rosária Dias Aires ◽  
Marina Ladeira ◽  
Silvia Guatimosim
Keyword(s):  
Respiratory System ◽  
Neurodegenerative Disorders ◽  
Therapeutic Agents ◽  
Fullerene Derivatives

Autophagy Modulators and Neuroinflammation

2020 ◽  
Vol 27 (6) ◽  
pp. 955-982 ◽  
Author(s):  
Kyoung Sang Cho ◽  
Jang Ho Lee ◽  
Jeiwon Cho ◽  
Guang-Ho Cha ◽  
Gyun Jee Song
Keyword(s):  
Neurodegenerative Disorders ◽  
Neurological Disorders ◽  
Mammalian Cells ◽  
Critical Role ◽  
Therapeutic Agents ◽  
Mechanisms Of Action ◽  
Scientific Interest ◽  
Therapeutic Tools ◽  
Underlying Mechanisms

Background: Neuroinflammation plays a critical role in the development and progression of various neurological disorders. Therefore, various studies have focused on the development of neuroinflammation inhibitors as potential therapeutic tools. Recently, the involvement of autophagy in the regulation of neuroinflammation has drawn substantial scientific interest, and a growing number of studies support the role of impaired autophagy in the pathogenesis of common neurodegenerative disorders. Objective: The purpose of this article is to review recent research on the role of autophagy in controlling neuroinflammation. We focus on studies employing both mammalian cells and animal models to evaluate the ability of different autophagic modulators to regulate neuroinflammation. Methods: We have mostly reviewed recent studies reporting anti-neuroinflammatory properties of autophagy. We also briefly discussed a few studies showing that autophagy modulators activate neuroinflammation in certain conditions. Results: Recent studies report neuroprotective as well as anti-neuroinflammatory effects of autophagic modulators. We discuss the possible underlying mechanisms of action of these drugs and their potential limitations as therapeutic agents against neurological disorders. Conclusion: Autophagy activators are promising compounds for the treatment of neurological disorders involving neuroinflammation.

scholarly journals Pharmaceutical Applications of Molecular Tweezers, Clefts and Clips

Molecules ◽  
2019 ◽  
Vol 24 (9) ◽  
pp. 1803 ◽  
Author(s):  
Amira Mbarek ◽  
Ghina Moussa ◽  
Jeanne Leblond Chain
Keyword(s):  
Cardiovascular Disease ◽  
Neurodegenerative Disorders ◽  
Therapeutic Agents ◽  
Mechanistic Studies ◽  
Molecular Tweezers ◽  
The Past ◽  
Pharmaceutical Applications ◽  
Controlled Motion

Synthetic acyclic receptors, composed of two arms connected with a spacer enabling molecular recognition, have been intensively explored in host-guest chemistry in the past decades. They fall into the categories of molecular tweezers, clefts and clips, depending on the geometry allowing the recognition of various guests. The advances in synthesis and mechanistic studies have pushed them forward to pharmaceutical applications, such as neurodegenerative disorders, infectious diseases, cancer, cardiovascular disease, diabetes, etc. In this review, we provide a summary of the synthetic molecular tweezers, clefts and clips that have been reported for pharmaceutical applications. Their structures, mechanism of action as well as in vitro and in vivo results are described. Such receptors were found to selectively bind biological guests, namely, nucleic acids, sugars, amino acids and proteins enabling their use as biosensors or therapeutics. Particularly interesting are dynamic molecular tweezers which are capable of controlled motion in response to an external stimulus. They proved their utility as imaging agents or in the design of controlled release systems. Despite some issues, such as stability, cytotoxicity or biocompatibility that still need to be addressed, it is obvious that molecular tweezers, clefts and clips are promising candidates for several incurable diseases as therapeutic agents, diagnostic or delivery tools.

scholarly journals SWS/NTE-dependent neuropathy is the model system to study neurodegeneration

2020 ◽  
Vol 26 ◽  
pp. 67-71
Author(s):  
N. P. Matiytsiv
Keyword(s):  
Life Expectancy ◽  
Life Span ◽  
Glial Cells ◽  
Neurodegenerative Disorders ◽  
Organophosphorus Compounds ◽  
Transmembrane Protein ◽  
Therapeutic Agents ◽  
Model System ◽  
Neuropathy Target Esterase ◽  
Swiss Cheese

Today there is many described neurodegenerative D. melanogaster mutants, which characterized by development of degenerative changes in brain. One of them are a swiss cheese (sws) gene mutants. Mutations in this gene causes apoptosis of neurons and hyperwrapping of their somas by the glial cells, reducing of life expectancy and decrease of locomotion. The sws gene is the ortholog of mammal’s neuropathy target esterase (NTE / PNPLA6). NTE is s neuronal, transmembrane protein, that possesses serinesterase activity, and can be the target for neurotoxic organophosphorus compounds activity. Mutations in PNPLA6 gene cause number hereditary neurodegenerative disorders, which nowadays are incurable. The search for therapeutic agents require use of model objects because researches on humans have both methodical and ethical limitations. During two last decades D. melanogaster has proven itself as a good model for study of neurodegenerative diseases. In this review, we described general characteristics of D. melanogaster gene sws, consequences of its mutations and provided evidences of high conservatism of gene product. Keywords: gene swiss cheese, neuropathy target esterase, neurodegeneration, brain, life span.

scholarly journals Engineering therapeutic protein disaggregases

2016 ◽  
Vol 27 (10) ◽  
pp. 1556-1560 ◽  
Author(s):  
James Shorter
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Neurodegenerative Disorders ◽  
Protein Misfolding ◽  
Therapeutic Agents ◽  
Loss Of Function ◽  
Native Structure ◽  
Aaa Atpase ◽  
Protein Misfolding And Aggregation ◽  
Small Molecule Enhancers ◽  
Lateral Sclerosis

Therapeutic agents are urgently required to cure several common and fatal neurodegenerative disorders caused by protein misfolding and aggregation, including amyotrophic lateral sclerosis (ALS), Parkinson’s disease (PD), and Alzheimer’s disease (AD). Protein disaggregases that reverse protein misfolding and restore proteins to native structure, function, and localization could mitigate neurodegeneration by simultaneously reversing 1) any toxic gain of function of the misfolded form and 2) any loss of function due to misfolding. Potentiated variants of Hsp104, a hexameric AAA+ ATPase and protein disaggregase from yeast, have been engineered to robustly disaggregate misfolded proteins connected with ALS (e.g., TDP-43 and FUS) and PD (e.g., α-synuclein). However, Hsp104 has no metazoan homologue. Metazoa possess protein disaggregase systems distinct from Hsp104, including Hsp110, Hsp70, and Hsp40, as well as HtrA1, which might be harnessed to reverse deleterious protein misfolding. Nevertheless, vicissitudes of aging, environment, or genetics conspire to negate these disaggregase systems in neurodegenerative disease. Thus, engineering potentiated human protein disaggregases or isolating small-molecule enhancers of their activity could yield transformative therapeutics for ALS, PD, and AD.

Nanotechnology-based Targeting of Neurodegenerative Disorders: A Promising Tool for Efficient Delivery of Neuromedicines

2020 ◽  
Vol 21 (8) ◽  
pp. 819-836
Author(s):  
Kuldeep Rajpoot
Keyword(s):  
Drug Delivery ◽  
Neurodegenerative Disorders ◽  
Therapeutic Agents ◽  
Carrier System ◽  
Efficient Treatment ◽  
Promising Tool ◽  
Therapeutic Benefits ◽  
Efficient Delivery ◽  
Traditional Drug ◽  
The Brain

Traditional drug delivery approaches remained ineffective in offering better treatment to various neurodegenerative disorders (NDs). In this context, diverse types of nanocarriers have shown their great potential to cross the blood-brain barrier (BBB) and have emerged as a prominent carrier system in drug delivery. Moreover, nanotechnology-based methods usually involve numerous nanosized carrier platforms, which potentiate the effect of the therapeutic agents in the therapy of NDs especially in diagnosis and drug delivery with negligible side effects. In addition, nanotechnology-based techniques have offered several strategies to cross BBB to intensify the bioavailability of drug moieties in the brain. In the last few years, diverse kinds of nanoparticles (NPs) have been developed by incorporating various biocompatible components (e.g., polysaccharide-based NPs, polymeric NPs, selenium NPs, AuNPs, protein-based NPs, gadolinium NPs, etc.), that showed great therapeutic benefits against NDs. Eventually, this review provides deep insights to explore recent applications of some innovative nanocarriers enclosing active molecules for the efficient treatment of NDs.

scholarly journals The other side of progestins: effects in the brain

2016 ◽  
Vol 57 (2) ◽  
pp. R109-R126 ◽  
Author(s):  
Silvia Giatti ◽  
Roberto Cosimo Melcangi ◽  
Marzia Pesaresi
Keyword(s):  
Nervous System ◽  
Neurodegenerative Disorders ◽  
Broad Class ◽  
Hormone Replacement ◽  
Therapeutic Agents ◽  
Chemical Structures ◽  
Contaminated Drinking Water ◽  
Aquatic Wildlife ◽  
The Brain ◽  
Different Doses

Progestins are a broad class of progestational agents widely differing in their chemical structures and pharmacological properties. Despite emerging data suggest that progestins, besides their action as endometrial protection, can also have multiple nonreproductive functions, much remains to be discovered regarding the actions exerted by these molecules in the nervous system. Here, we report the role exerted by different progestins, currently used for contraception or in postmenopausal hormone replacement therapies, in regulating cognitive functions as well as social behavior and mood. We provide evidence that the effects and mechanisms underlying their actions are still confusing due to the use of different estrogens and progestins as well as different doses, duration of exposure, route of administration, baseline hormonal status and age of treated women. We also discuss the emerging issue concerning the relevant increase of these substances in the environment, able to deeply affect aquatic wildlife as well as to exert a possible influence in humans, which may be exposed to these compounds via contaminated drinking water and seafood. Finally, we report literature data showing the neurobiological action of progestins and in particular their importance during neurodegenerative events. This is extremely interesting, since some of the progestins currently used in clinical practice exert neuroprotective and anti-inflammatory effects in the nervous system, opening new promising opportunities for the use of these molecules as therapeutic agents for trauma and neurodegenerative disorders.

scholarly journals MicroRNAs in Huntington’s Disease: Diagnostic Biomarkers or Therapeutic Agents?

2021 ◽  
Vol 15 ◽  
Author(s):  
Xiaoyu Dong ◽  
Shuyan Cong
Keyword(s):  
Nervous System ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Small Molecule ◽  
Mirna Expression ◽  
Neurodegenerative Disorders ◽  
Therapeutic Agents ◽  
Diagnostic Biomarkers ◽  
Growth Development

MicroRNA (miRNA) is a non-coding single-stranded small molecule of approximately 21 nucleotides. It degrades or inhibits the translation of RNA by targeting the 3′-UTR. The miRNA plays an important role in the growth, development, differentiation, and functional execution of the nervous system. Dysregulated miRNA expression has been associated with several pathological processes of neurodegenerative disorders, including Huntington’s disease (HD). Recent studies have suggested promising roles of miRNAs as biomarkers and potential therapeutic targets for HD. Here, we review the emerging role of dysregulated miRNAs in HD and describe general biology of miRNAs, their pathophysiological implications, and their potential roles as biomarkers and therapeutic agents.

Iron chelation as a potential therapy for neurodegenerative disease

2008 ◽  
Vol 36 (6) ◽  
pp. 1304-1308 ◽  
Author(s):  
Robert C. Hider ◽  
Yongmin Ma ◽  
Francisco Molina-Holgado ◽  
Alessandra Gaeta ◽  
Sourav Roy
Keyword(s):  
Oxidative Stress ◽  
Neurodegenerative Disorders ◽  
Rational Design ◽  
Chelation Therapy ◽  
Iron Chelation ◽  
Therapeutic Agents ◽  
Disease States ◽  
Pathological Conditions ◽  
Pharmacological Targets ◽  
And Oxidative Stress

Neurodegenerative disorders include a variety of pathological conditions, which share similar critical metabolic processes such as protein aggregation and oxidative stress, both of which are associated with the involvement of metal ions. Chelation therapy could provide a valuable therapeutic approach to such disease states, since metals, particularly iron, are realistic pharmacological targets for the rational design of new therapeutic agents.

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