Subcellular Localization of Copper—Cellular Bioimaging with Focus on Neurological Disorders

As an essential trace element, copper plays a pivotal role in physiological body functions. In fact, dysregulated copper homeostasis has been clearly linked to neurological disorders including Wilson and Alzheimer’s disease. Such neurodegenerative diseases are associated with progressive loss of neurons and thus impaired brain functions. However, the underlying mechanisms are not fully understood. Characterization of the element species and their subcellular localization is of great importance to uncover cellular mechanisms. Recent research activities focus on the question of how copper contributes to the pathological findings. Cellular bioimaging of copper is an essential key to accomplish this objective. Besides information on the spatial distribution and chemical properties of copper, other essential trace elements can be localized in parallel. Highly sensitive and high spatial resolution techniques such as LA-ICP-MS, TEM-EDS, S-XRF and NanoSIMS are required for elemental mapping on subcellular level. This review summarizes state-of-the-art techniques in the field of bioimaging. Their strengths and limitations will be discussed with particular focus on potential applications for the elucidation of copper-related diseases. Based on such investigations, further information on cellular processes and mechanisms can be derived under physiological and pathological conditions. Bioimaging studies might enable the clarification of the role of copper in the context of neurodegenerative diseases and provide an important basis to develop therapeutic strategies for reduction or even prevention of copper-related disorders and their pathological consequences.

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Redox Homeostasis and Prospects for Therapeutic Targeting in Neurodegenerative Disorders

Oxidative Medicine and Cellular Longevity ◽

10.1155/2021/9971885 ◽

2021 ◽

Vol 2021 ◽

pp. 1-14

Author(s):

Musbau Adewumi Akanji ◽

Damilare Emmanuel Rotimi ◽

Tobiloba Christiana Elebiyo ◽

Oluwakemi Josephine Awakan ◽

Oluyomi Stephen Adeyemi

Keyword(s):

Neurodegenerative Diseases ◽

Neurodegenerative Disorders ◽

Redox Homeostasis ◽

Reactive Species ◽

Cellular Damage ◽

Cellular Mechanisms ◽

Cellular Redox ◽

Redox Imbalance ◽

Cellular Processes ◽

The Brain

Reactive species, such as those of oxygen, nitrogen, and sulfur, are considered part of normal cellular metabolism and play significant roles that can impact several signaling processes in ways that lead to either cellular sustenance, protection, or damage. Cellular redox processes involve a balance in the production of reactive species (RS) and their removal because redox imbalance may facilitate oxidative damage. Physiologically, redox homeostasis is essential for the maintenance of many cellular processes. RS may serve as signaling molecules or cause oxidative cellular damage depending on the delicate equilibrium between RS production and their efficient removal through the use of enzymatic or nonenzymatic cellular mechanisms. Moreover, accumulating evidence suggests that redox imbalance plays a significant role in the progression of several neurodegenerative diseases. For example, studies have shown that redox imbalance in the brain mediates neurodegeneration and alters normal cytoprotective responses to stress. Therefore, this review describes redox homeostasis in neurodegenerative diseases with a focus on Alzheimer’s and Parkinson’s disease. A clearer understanding of the redox-regulated processes in neurodegenerative disorders may afford opportunities for newer therapeutic strategies.

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The Influence of Vitamin D on Neurodegeneration and Neurological Disorders: A Rationale for its Physio-pathological Actions

Current Pharmaceutical Design ◽

10.2174/1381612826666200316145725 ◽

2020 ◽

Vol 26 (21) ◽

pp. 2475-2491 ◽

Cited By ~ 1

Author(s):

Maria Morello ◽

Massimo Pieri ◽

Rossella Zenobi ◽

Alessandra Talamo ◽

Delphine Stephan ◽

...

Keyword(s):

Multiple Sclerosis ◽

Vitamin D ◽

Neurodegenerative Diseases ◽

Neurological Disorders ◽

Neurological Diseases ◽

Steroid Hormone ◽

Neuroactive Steroid ◽

Brain Functions ◽

Prevention And Treatment ◽

Lateral Sclerosis

Vitamin D is a steroid hormone implicated in the regulation of neuronal integrity and many brain functions. Its influence, as a nutrient and a hormone, on the physiopathology of the most common neurodegenerative diseases is continuously emphasized by new studies. This review addresses what is currently known about the action of vitamin D on the nervous system and neurodegenerative diseases such as Multiple Sclerosis, Alzheimer’s disease, Parkinson’s disease and Amyotrophic Lateral Sclerosis. Further vitamin D research is necessary to understand how the action of this “neuroactive” steroid can help to optimize the prevention and treatment of several neurological diseases.

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The Cross Talk between Underlying Mechanisms of Multiple Sclerosis and Epilepsy May Provide New Insights for More Efficient Therapies

Pharmaceuticals ◽

10.3390/ph14101031 ◽

2021 ◽

Vol 14 (10) ◽

pp. 1031

Author(s):

Atefeh Rayatpour ◽

Sahar Farhangi ◽

Ester Verdaguer ◽

Jordi Olloquequi ◽

Jesus Ureña ◽

...

Keyword(s):

Multiple Sclerosis ◽

General Population ◽

Neurodegenerative Diseases ◽

Cross Talk ◽

Huntington Disease ◽

Neurological Disorders ◽

Epileptic Seizures ◽

Bidirectional Association ◽

The Common ◽

Underlying Mechanisms

Despite the significant differences in pathological background of neurodegenerative diseases, epileptic seizures are a comorbidity in many disorders such as Huntington disease (HD), Alzheimer’s disease (AD), and multiple sclerosis (MS). Regarding the last one, specifically, it has been shown that the risk of developing epilepsy is three to six times higher in patients with MS compared to the general population. In this context, understanding the pathological processes underlying this connection will allow for the targeting of the common and shared pathological pathways involved in both conditions, which may provide a new avenue in the management of neurological disorders. This review provides an outlook of what is known so far about the bidirectional association between epilepsy and MS.

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Flavonoids in the Treatment of Alzheimer’s and Other Neurodegenerative Diseases

Current Medicinal Chemistry ◽

10.2174/0929867325666180209132125 ◽

2018 ◽

Vol 25 (27) ◽

pp. 3228-3246 ◽

Cited By ~ 20

Author(s):

Cristina Airoldi ◽

Barbara La Ferla ◽

Giuseppe D`Orazio ◽

Carlotta Ciaramelli ◽

Alessandro Palmioli

Keyword(s):

Neurodegenerative Diseases ◽

Biological Activities ◽

Chemical Properties ◽

New Drugs ◽

Terrestrial Plants ◽

Positive Effects ◽

Brain Functions ◽

Age Related ◽

Physico Chemical ◽

Almost All

Flavonoids are phytochemicals present in almost all terrestrial plants and, as a consequence, in plant-based foods, and thus consumed by humans through diet. Recent evidences suggest that several flavonoids have positive effects against dementia and Alzheimer’s disease, reversing age-related declines in neurocognitive performances. In this review, we provide a general classification of natural and synthetic flavonoids, a description of their physico-chemical properties, in particular their redox properties and stability, and an extensive overview about their biological activities and structure-activity relationship in the field of neurodegenerative diseases. In addition, a section will be dedicated to the synthetic strategies for the preparation of bioactive derivatives. This information will be essential for the design and development of new drugs that can improve brain functions.

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Autophagy Modulators and Neuroinflammation

Current Medicinal Chemistry ◽

10.2174/0929867325666181031144605 ◽

2020 ◽

Vol 27 (6) ◽

pp. 955-982 ◽

Cited By ~ 4

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.

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Molecular and Cellular Mechanisms of Metformin in Cervical Cancer

Cancers ◽

10.3390/cancers13112545 ◽

2021 ◽

Vol 13 (11) ◽

pp. 2545

Author(s):

Ya-Hui Chen ◽

Po-Hui Wang ◽

Pei-Ni Chen ◽

Shun-Fa Yang ◽

Yi-Hsuan Hsiao

Keyword(s):

Cervical Cancer ◽

Potential Role ◽

Treatment Options ◽

Cellular Mechanisms ◽

Anticancer Effects ◽

Clinical Benefits ◽

Underlying Mechanisms

Cervical cancer is one of the major gynecologic malignancies worldwide. Treatment options include chemotherapy, surgical resection, radiotherapy, or a combination of these treatments; however, relapse and recurrence may occur, and the outcome may not be favorable. Metformin is an established, safe, well-tolerated drug used in the treatment of type 2 diabetes; it can be safely combined with other antidiabetic agents. Diabetes, possibly associated with an increased site-specific cancer risk, may relate to the progression or initiation of specific types of cancer. The potential effects of metformin in terms of cancer prevention and therapy have been widely studied, and a number of studies have indicated its potential role in cancer treatment. The most frequently proposed mechanism underlying the diabetes–cancer association is insulin resistance, which leads to secondary hyperinsulinemia; furthermore, insulin may exert mitogenic effects through the insulin-like growth factor 1 (IGF-1) receptor, and hyperglycemia may worsen carcinogenesis through the induction of oxidative stress. Evidence has suggested clinical benefits of metformin in the treatment of gynecologic cancers. Combining current anticancer drugs with metformin may increase their efficacy and diminish adverse drug reactions. Accumulating evidence is indicating that metformin exerts anticancer effects alone or in combination with other agents in cervical cancer in vitro and in vivo. Metformin might thus serve as an adjunct therapeutic agent for cervical cancer. Here, we reviewed the potential anticancer effects of metformin against cervical cancer and discussed possible underlying mechanisms.

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Crosstalk between Different DNA Repair Pathways Contributes to Neurodegenerative Diseases

Biology ◽

10.3390/biology10020163 ◽

2021 ◽

Vol 10 (2) ◽

pp. 163

Author(s):

Swapnil Gupta ◽

Panpan You ◽

Tanima SenGupta ◽

Hilde Nilsen ◽

Kulbhushan Sharma

Keyword(s):

Dna Repair ◽

Neurodegenerative Diseases ◽

3D Models ◽

Model Systems ◽

Spinocerebellar Ataxias ◽

C Elegans ◽

Cellular Processes ◽

Age Related ◽

Damage Response ◽

Lateral Sclerosis

Genomic integrity is maintained by DNA repair and the DNA damage response (DDR). Defects in certain DNA repair genes give rise to many rare progressive neurodegenerative diseases (NDDs), such as ocular motor ataxia, Huntington disease (HD), and spinocerebellar ataxias (SCA). Dysregulation or dysfunction of DDR is also proposed to contribute to more common NDDs, such as Parkinson’s disease (PD), Alzheimer’s disease (AD), and Amyotrophic Lateral Sclerosis (ALS). Here, we present mechanisms that link DDR with neurodegeneration in rare NDDs caused by defects in the DDR and discuss the relevance for more common age-related neurodegenerative diseases. Moreover, we highlight recent insight into the crosstalk between the DDR and other cellular processes known to be disturbed during NDDs. We compare the strengths and limitations of established model systems to model human NDDs, ranging from C. elegans and mouse models towards advanced stem cell-based 3D models.

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Immunomodulatory Nanomedicine for the Treatment of Atherosclerosis

Journal of Clinical Medicine ◽

10.3390/jcm10143185 ◽

2021 ◽

Vol 10 (14) ◽

pp. 3185

Author(s):

Linsey J. F. Peters ◽

Alexander Jans ◽

Matthias Bartneck ◽

Emiel P. C. van der Vorst

Keyword(s):

Cell Proliferation ◽

Drug Carriers ◽

Research Field ◽

General Introduction ◽

Cellular Receptors ◽

Cellular Processes ◽

Potential Applications ◽

Current Therapies ◽

Based Medicine ◽

Physiological Systems

Atherosclerosis is the main underlying cause of cardiovascular diseases (CVDs), which remain the number one contributor to mortality worldwide. Although current therapies can slow down disease progression, no treatment is available that can fully cure or reverse atherosclerosis. Nanomedicine, which is the application of nanotechnology in medicine, is an emerging field in the treatment of many pathologies, including CVDs. It enables the production of drugs that interact with cellular receptors, and allows for controlling cellular processes after entering these cells. Nanomedicine aims to repair, control and monitor biological and physiological systems via nanoparticles (NPs), which have been shown to be efficient drug carriers. In this review we will, after a general introduction, highlight the advantages and limitations of the use of such nano-based medicine, the potential applications and targeting strategies via NPs. For example, we will provide a detailed discussion on NPs that can target relevant cellular receptors, such as integrins, or cellular processes related to atherogenesis, such as vascular smooth muscle cell proliferation. Furthermore, we will underline the (ongoing) clinical trials focusing on NPs in CVDs, which might bring new insights into this research field.

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Roles of Microglial Ion Channel in Neurodegenerative Diseases

Journal of Clinical Medicine ◽

10.3390/jcm10061239 ◽

2021 ◽

Vol 10 (6) ◽

pp. 1239

Author(s):

Alexandru Cojocaru ◽

Emilia Burada ◽

Adrian-Tudor Bălșeanu ◽

Alexandru-Florian Deftu ◽

Bogdan Cătălin ◽

...

Keyword(s):

Ion Channels ◽

Neurodegenerative Diseases ◽

Excitable Cells ◽

Proton Channels ◽

Voltage Gated ◽

Cellular Processes ◽

Pathological Conditions ◽

The Common ◽

Transient Receptor ◽

The Impact

As the average age and life expectancy increases, the incidence of both acute and chronic central nervous system (CNS) pathologies will increase. Understanding mechanisms underlying neuroinflammation as the common feature of any neurodegenerative pathology, we can exploit the pharmacology of cell specific ion channels to improve the outcome of many CNS diseases. As the main cellular player of neuroinflammation, microglia play a central role in this process. Although microglia are considered non-excitable cells, they express a variety of ion channels under both physiological and pathological conditions that seem to be involved in a plethora of cellular processes. Here, we discuss the impact of modulating microglia voltage-gated, potential transient receptor, chloride and proton channels on microglial proliferation, migration, and phagocytosis in neurodegenerative diseases.

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Composite Poly(vinyl alcohol)-Based Nanofibers Embedding Differently-Shaped Gold Nanoparticles: Preparation and Characterization

Polymers ◽

10.3390/polym13101604 ◽

2021 ◽

Vol 13 (10) ◽

pp. 1604

Author(s):

Andrea Dodero ◽

Maila Castellano ◽

Paola Lova ◽

Massimo Ottonelli ◽

Elisabetta Brunengo ◽

...

Keyword(s):

Vinyl Alcohol ◽

Ad Hoc ◽

Chemical Reduction ◽

Chemical Properties ◽

Single Step ◽

Gold Nanostructures ◽

Poly Vinyl Alcohol ◽

Spherical Nanoparticles ◽

Potential Applications ◽

New Perspective

Poly(vinyl alcohol) nanofibrous mats containing ad hoc synthesized gold nanostructures were prepared via a single-step electrospinning procedure and investigated as a novel composite platform with several potential applications. Specifically, the effect of differently shaped and sized gold nanostructures on the resulting mat physical-chemical properties was investigated. In detail, nearly spherical nanoparticles and nanorods were first synthesized through a chemical reduction of gold precursors in water by using (hexadecyl)trimethylammonium bromide as the stabilizing agent. These nanostructures were then dispersed in poly(vinyl alcohol) aqueous solutions to prepare nanofibrous mats, which were then stabilized via a humble thermal treatment able to enhance their thermal stability and water resistance. Remarkably, the nanostructure type was proven to influence the mesh morphology, with the small spherical nanoparticles and the large nanorods leading to thinner well defined or bigger defect-rich nanofibers, respectively. Finally, the good mechanical properties shown by the prepared composite mats suggest their ease of handleability thereby opening new perspective applications.

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