scholarly journals Modulation of serine/threonine phosphatases by melatonin: therapeutic approaches in neurodegenerative diseases

2018 ◽  
Vol 175 (16) ◽  
pp. 3220-3229 ◽  
Author(s):  
Raquel L Arribas ◽  
Alejandro Romero ◽  
Javier Egea ◽  
Cristóbal de los Ríos
Keyword(s):  
Neurodegenerative Diseases ◽  
Therapeutic Approaches

Nanotheranostic agents for neurodegenerative diseases

2020 ◽  
Vol 4 (6) ◽  
pp. 645-675
Author(s):  
Parasuraman Padmanabhan ◽  
Mathangi Palanivel ◽  
Ajay Kumar ◽  
Domokos Máthé ◽  
George K. Radda ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Neurodegenerative Diseases ◽  
Cell Types ◽  
Specific Cell ◽  
Ageing Population ◽  
Target Tissue ◽  
Therapeutic Approaches ◽  
Surface Receptors ◽  
Theranostic Agents ◽  
Preclinical Animal Models

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.

Multitarget therapeutic approaches for Alzheimer's and Parkinson's diseases: an opportunity or an illusion?

2021 ◽  
Author(s):  
Maria João Matos
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neurodegenerative Diseases ◽  
Therapeutic Options ◽  
Therapeutic Approaches ◽  
Recent Information ◽  
Temporary Relief ◽  
Parkinson’S Diseases ◽  
Innovative Approaches

Alzheimer's and Parkinson's disease are the most prevalent neurodegenerative diseases and the leading causes of dementia worldwide. The etiology of these multifactorial pathologies is not completely known. The available therapeutic approaches can cause temporary relief of symptoms but cannot slow down their progression or cure them. Life-changing therapeutic solutions are urgently needed, as the number of people suffering from these pathologies has been increasing quickly over the last few decades. Several targets are being studied, and innovative approaches are being pursued to find new therapeutic options. This overview is focused on the most recent information regarding the paradigm of using multitarget compounds to treat both Alzheimer's and Parkinson's disease.

Cellular responses following retinal injuries and therapeutic approaches for neurodegenerative diseases

2014 ◽  
Vol 43 ◽  
pp. 17-75 ◽  
Author(s):  
Nicolás Cuenca ◽  
Laura Fernández-Sánchez ◽  
Laura Campello ◽  
Victoria Maneu ◽  
Pedro De la Villa ◽  
...  
Keyword(s):  
Neurodegenerative Diseases ◽  
Cellular Responses ◽  
Therapeutic Approaches

Underlying mechanisms and chemical/biochemical therapeutic approaches to ameliorate protein misfolding neurodegenerative diseases

BioFactors ◽  
2016 ◽  
Vol 43 (6) ◽  
pp. 737-759 ◽  
Author(s):  
Seyedhossein Hekmatimoghaddam ◽  
Mohamad Reza Zare-Khormizi ◽  
Fatemeh Pourrajab
Keyword(s):  
Neurodegenerative Diseases ◽  
Protein Misfolding ◽  
Therapeutic Approaches ◽  
Underlying Mechanisms

scholarly journals Nuclear Receptors as Therapeutic Targets for Neurodegenerative Diseases: Lost in Translation

2019 ◽  
Vol 59 (1) ◽  
pp. 237-261 ◽  
Author(s):  
Miguel Moutinho ◽  
Juan F. Codocedo ◽  
Shweta S. Puntambekar ◽  
Gary E. Landreth
Keyword(s):  
Animal Models ◽  
Neurodegenerative Diseases ◽  
Nuclear Receptors ◽  
Motor Impairment ◽  
Therapeutic Approaches ◽  
New Findings ◽  
Wide Range ◽  
Preclinical And Clinical Studies ◽  
Lost In Translation

Neurodegenerative diseases are characterized by a progressive loss of neurons that leads to a broad range of disabilities, including severe cognitive decline and motor impairment, for which there are no effective therapies. Several lines of evidence support a putative therapeutic role of nuclear receptors (NRs) in these types of disorders. NRs are ligand-activated transcription factors that regulate the expression of a wide range of genes linked to metabolism and inflammation. Although the activation of NRs in animal models of neurodegenerative disease exhibits promising results, the translation of this strategy to clinical practice has been unsuccessful. In this review we discuss the role of NRs in neurodegenerative diseases in light of preclinical and clinical studies, as well as new findings derived from the analysis of transcriptomic databases from humans and animal models. We discuss the failure in the translation of NR-based therapeutic approaches and consider alternative and novel research avenues in the development of effective therapies for neurodegenerative diseases.

scholarly journals Influence of Commensal Microbiota on the Enteric Nervous System and Its Role in Neurodegenerative Diseases

2018 ◽  
Vol 10 (3) ◽  
pp. 172-180 ◽  
Author(s):  
Kristina Endres ◽  
Karl-Herbert Schäfer
Keyword(s):  
Nervous System ◽  
Neurodegenerative Diseases ◽  
Enteric Nervous System ◽  
The Other ◽  
Therapeutic Approaches ◽  
Commensal Microbiota ◽  
Open Questions ◽  
Learning Capabilities ◽  
The Central Nervous System ◽  
Parkinson Diseases

When thinking about neurodegenerative diseases, the first symptoms that come to mind are loss of memory and learning capabilities, which all resemble hallmarks of manifestation of such diseases in the central nervous system (CNS). However, the gut comprises the largest nervous system outside the CNS that is autonomously active and in close interplay with its microbiota. Therefore, the enteric nervous system (ENS) might serve as an indicator of degenerative pathomechanisms that also affect the CNS. On the other hand, it might offer an entry point for devastating influences from the microbial community or – conversely – for therapeutic approaches via gut commensals. Within the last years, the ENS and gut microbiota therefore have sparked the interest of researchers of CNS diseases and we here report on recent findings and open questions, especially with regard to Alzheimer and Parkinson diseases.

scholarly journals Isomeric O-methyl cannabidiolquinones with dual BACH1/NRF2 activity

2020 ◽  
Author(s):  
Laura Casares ◽  
Juan Diego Unciti ◽  
Maria Eugenia Prados ◽  
Diego Caprioglio ◽  
Maureen Higgins ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Multiple Sclerosis ◽  
Neurodegenerative Diseases ◽  
Cell Models ◽  
Therapeutic Approaches ◽  
Neuroprotective Effects ◽  
Anti Oxidant ◽  
Anti Inflammatory ◽  
The Brain

ABSTRACTOxidative stress and inflammation in the brain are two key hallmarks of neurodegenerative diseases (NDs) such as Alzheimer’s, Parkinson’s, Huntington’s and multiple sclerosis. The axis NRF2-BACH1 has anti-inflammatory and anti-oxidant properties that could be exploited pharmacologically to obtain neuroprotective effects. Activation of NRF2 or inhibition of BACH1 are, individually, promising therapeutic approaches for NDs. Compounds with dual activity as NRF2 activators and BACH1 inhibitors, could therefore potentially provide a more robust antioxidant and anti-inflammatory effects, with an overall better neuroprotective outcome. The phytocannabinoid cannabidiol (CBD) inhibits BACH1 but lacks significant NRF2 activating properties. Based on this scaffold, we have developed a novel CBD derivative that is highly effective at both inhibiting BACH1 and activating NRF2. This new CBD derivative provides neuroprotection in cell models of relevance to Huntington’s disease, setting the basis for further developments in vivo.

scholarly journals Modulation of Neuroinflammation by the Gut Microbiota in Prion and Prion-Like Diseases

Pathogens ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 887
Author(s):  
Josephine Trichka ◽  
Wen-Quan Zou
Keyword(s):  
Nervous System ◽  
Gut Microbiota ◽  
Neurodegenerative Diseases ◽  
Neurodegenerative Disease ◽  
Peripheral Nervous System ◽  
Brain Parenchyma ◽  
Therapeutic Approaches ◽  
Microbial Metabolite ◽  
The Past

The process of neuroinflammation contributes to the pathogenic mechanism of many neurodegenerative diseases. The deleterious attributes of neuroinflammation involve aberrant and uncontrolled activation of glia, which can result in damage to proximal brain parenchyma. Failure to distinguish self from non-self, as well as leukocyte reaction to aggregation and accumulation of proteins in the CNS, are the primary mechanisms by which neuroinflammation is initiated. While processes local to the CNS may instigate neurodegenerative disease, the existence or dysregulation of systemic homeostasis can also serve to improve or worsen CNS pathologies, respectively. One fundamental component of systemic homeostasis is the gut microbiota, which communicates with the CNS via microbial metabolite production, the peripheral nervous system, and regulation of tryptophan metabolism. Over the past 10–15 years, research focused on the microbiota–gut–brain axis has culminated in the discovery that dysbiosis, or an imbalance between commensal and pathogenic gut bacteria, can promote CNS pathologies. Conversely, a properly regulated and well-balanced microbiome supports CNS homeostasis and reduces the incidence and extent of pathogenic neuroinflammation. This review will discuss the role of the gut microbiota in exacerbating or alleviating neuroinflammation in neurodegenerative diseases, and potential microbiota-based therapeutic approaches to reduce pathology in diseased states.

scholarly journals Spotlight on Neuroimmunology: Illustrations from Neurodegenerative Diseases

2017 ◽  
Vol 6 (2) ◽  
pp. 146
Author(s):  
Abdelaziz Ghanemi ◽  
Besma Boubertakh
Keyword(s):  
Nervous System ◽  
Immune System ◽  
Neurodegenerative Diseases ◽  
Immune Functions ◽  
Therapeutic Approaches ◽  
Research Methodologies ◽  
New Therapeutic Approaches ◽  
Diagnostic Approaches ◽  
Important Field

<span lang="EN-US">The immune system plays key roles in the defense of the organism. However, the effects of the immune system are not limited to the immune functions and have impacts beyond the anti-pathogenes role.                          Indeed, neuroimmunology is a representative field of how the immune system affects non-immune biological and physio-pathological functions. Herein, we have selected a number of neurodegenerative diseases as illustrative examples to put a spotlight on this important field.              Importantly, clarifying the links and interactions between the immune system and the nervous system represents key elements for the understanding neurodegenerative diseases since it will lead to new theories about the pathogenesis and the mechanisms underlying the related processes and thus, provide us with new data and novel tools to both describe the related pathways and develop new therapeutic approaches as well as diagnostic approaches and research methodologies based on such new discoveries.</span>

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