The close link between brain vascular pathological conditions and neurodegenerative diseases: Focus on some examples and potential treatments

2021 ◽  
pp. 106951
Author(s):  
Giuseppe Schirò ◽  
Carmela Rita Balistreri
Keyword(s):  
Neurodegenerative Diseases ◽  
Close Link ◽  
Pathological Conditions

scholarly journals Roles of Microglial Ion Channel in Neurodegenerative Diseases

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.

scholarly journals Coenzyme Q10 and its effects in the treatment of neurodegenerative diseases

2009 ◽  
Vol 45 (4) ◽  
pp. 607-618 ◽  
Author(s):  
Graciela Cristina dos Santos ◽  
Lusânia Maria Greggi Antunes ◽  
Antonio Cardozo dos Santos ◽  
Maria de Lourdes Pires Bianchi
Keyword(s):  
Neurodegenerative Diseases ◽  
Health Risks ◽  
Coenzyme Q10 ◽  
Cellular Respiration ◽  
Irreversible Loss ◽  
Beneficial Effects ◽  
Pathological Conditions ◽  
Electron Transportation ◽  
The Brain ◽  
Lateral Sclerosis

According to clinical and pre-clinical studies, oxidative stress and its consequences may be the cause or, at least, a contributing factor, to a large number of neurodegenerative diseases. These diseases include common and debilitating disorders, characterized by progressive and irreversible loss of neurons in specific regions of the brain. The most common neurodegenerative diseases are Parkinson's disease, Huntington's disease, Alzheimer's disease and amyotrophic lateral sclerosis. Coenzyme Q10 (CoQ10) has been extensively studied since its discovery in 1957. It is a component of the electron transportation chain and participates in aerobic cellular respiration, generating energy in the form of adenosine triphosphate (ATP). The property of CoQ10 to act as an antioxidant or a pro-oxidant, suggests that it also plays an important role in the modulation of redox cellular status under physiological and pathological conditions, also performing a role in the ageing process. In several animal models of neurodegenerative diseases, CoQ10 has shown beneficial effects in reducing disease progression. However, further studies are needed to assess the outcome and effectiveness of CoQ10 before exposing patients to unnecessary health risks at significant costs.

scholarly journals The Emerging Role of Neural Cell-Derived Exosomes in Intercellular Communication in Health and Neurodegenerative Diseases

2021 ◽  
Vol 15 ◽  
Author(s):  
Luyao Huo ◽  
Xinzhe Du ◽  
Xinrong Li ◽  
Sha Liu ◽  
Yong Xu
Keyword(s):  
Neurodegenerative Diseases ◽  
Intercellular Communication ◽  
Neural Cells ◽  
Stress Effect ◽  
Brain Growth ◽  
Bioactive Substances ◽  
Pathological Conditions ◽  
Specific Proteins ◽  
The Central Nervous System

Intercellular communication in the central nervous system (CNS) is essential for brain growth, development, and homeostasis maintenance and, when dysfunctional, is involved in the occurrence and development of neurodegenerative diseases. Increasing evidence indicates that extracellular vesicles, especially exosomes, are critical mediators of intercellular signal transduction. Under physiological and pathological conditions, neural cells secret exosomes with the influence of many factors. These exosomes can carry specific proteins, lipids, nucleic acids, and other bioactive substances to the recipient cells to regulate their function. Depending on the CNS environment, as well as the origin and physiological or pathological status of parental cells, exosomes can mediate a variety of different effects, including synaptic plasticity, nutritional metabolic support, nerve regeneration, inflammatory response, anti-stress effect, cellular waste disposal, and the propagation of toxic components, playing an important role in health and neurodegenerative diseases. This review will discuss the possible roles of exosomes in CNS intercellular communication in both physiologic and neurodegenerative conditions.

scholarly journals Homocysteine and Asymmetric Dimethylarginine (ADMA) in Neurological Diseases

2017 ◽  
Vol 6 (2) ◽  
pp. 930-939
Author(s):  
Jolanta Dorszewska
Keyword(s):  
Neurodegenerative Diseases ◽  
Metabolic Pathways ◽  
Asymmetric Dimethylarginine ◽  
Neurological Diseases ◽  
No Synthase ◽  
Lipid Lowering ◽  
Endogenous Inhibitor ◽  
Pathological Conditions ◽  
The Family ◽  
Key Factor

Homocysteine (Hcy) is formed from methionine (Met) and is distributed in two metabolic pathways: in the process of remethylation to Met and in the process of transsulfuration to cysteine. Hyperhomocysteinemia (HHcy) is a risk factor for cardiovascular and neurological diseases such as: Alzheimer’s and Parkinson’s diseases, multiple sclerosis, and stroke. Increased Hcy level may lead to endothelial dysfunction due to impaired bioavailability of endothelium-derived nitric oxide (NO). The molecular mechanism decreasing the levels of NO in HHcy conditions is incompletely understood, but it seems that asymmetric dimethylarginine (ADMA), an endogenous inhibitor of NO synthase, may be a key factor. ADMA is formed from L-arginine by enzymes in the family of protein N-methyltransferases (PRMT) and may undergo hydrolysis to L-citrulline and dimethylamine with the participation of dimethylaminohydrolase (DDAH). In pathological conditions such as neurodegenerative diseases, Hcy may lead to increased ADMA concentrations by inhibiting the activity of DDAH. Several drugs, such L-dopa, antiepileptic drugs, and lipid-lowering drugs, may interfere with the metabolic pathways of thiols, leading to an alteration of plasma Hcy and ADMA levels. It seems that administration of L-arginine, in conjunction with B vitamins, to patients with HHcy may be a new method in the treatment of neurodegenerative diseases.

scholarly journals Peroxisomes in intracellular cholesterol transport: from basic physiology to brain pathology

2021 ◽  
Vol 1 (2) ◽  
Author(s):  
Jian Xiao ◽  
Bao-Liang Song ◽  
Jie Luo
Keyword(s):  
Neurodegenerative Diseases ◽  
Cholesterol Homeostasis ◽  
Neurological Deficits ◽  
Cholesterol Transport ◽  
Peroxisome Biogenesis ◽  
Cholesterol Trafficking ◽  
Cholesterol Accumulation ◽  
Peroxisomal Disorders ◽  
Pathological Conditions ◽  
Ether Phospholipids

Peroxisomes are actively involved in the metabolism of various lipids including fatty acids, ether phospholipids, bile acids as well as the processing of reactive oxygen and nitrogen species. Recent studies show that peroxisomes can regulate cholesterol homeostasis by mediating cholesterol transport from the lysosomes to the endoplasmic reticulum and towards primary cilium as well. Disruptions of peroxisome biogenesis or functions lead to peroxisomal disorders that usually involve neurological deficits. Peroxisomal dysfunction is also linked to several neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease. In many peroxisomal disorders and neurodegenerative diseases, aberrant cholesterol accumulation is frequently encountered yet largely neglected. This review discusses the current understanding of the mechanisms by which peroxisomes facilitate cholesterol trafficking within the cell and the pathological conditions related to impaired cholesterol transport by peroxisomes, with the hope to inspire future development of the treatments for peroxisomal disorders and neurodegenerative diseases.

scholarly journals The Role of GPNMB in Inflammation

2021 ◽  
Vol 12 ◽  
Author(s):  
Marina Saade ◽  
Giovanna Araujo de Souza ◽  
Cristoforo Scavone ◽  
Paula Fernanda Kinoshita
Keyword(s):  
Neurodegenerative Diseases ◽  
Innate Immune ◽  
Inflammatory Conditions ◽  
Pathological Conditions ◽  
Published Evidence ◽  
The Central Nervous System ◽  
Inflammation Resolution ◽  
The Brain ◽  
Lps Treatment

Inflammation is a response to a lesion in the tissue or infection. This process occurs in a specific manner in the central nervous system and is called neuroinflammation, which is involved in neurodegenerative diseases. GPNMB, an endogenous glycoprotein, has been recently related to inflammation and neuroinflammation. GPNMB is highly expressed in macrophages and microglia, which are cells involved with innate immune response in the periphery and the brain, respectively. Some studies have shown increased levels of GPNMB in pro-inflammatory conditions, such as LPS treatment, and in pathological conditions, such as neurodegenerative diseases and cancer. However, the role of GPNMB in inflammation is still not clear. Even though most studies suggest that GPNMB might have an anti-inflammatory role by promoting inflammation resolution, there is evidence that GPNMB could be pro-inflammatory. In this review, we gather and discuss the published evidence regarding this interaction.

To be or not to be cell autonomous? Autophagy says both

2017 ◽  
Vol 61 (6) ◽  
pp. 649-661 ◽  
Author(s):  
Nina Fenouille ◽  
Anna Chiara Nascimbeni ◽  
Joëlle Botti-Millet ◽  
Nicolas Dupont ◽  
Etienne Morel ◽  
...  
Keyword(s):  
Amino Acids ◽  
Fatty Acids ◽  
Neurodegenerative Diseases ◽  
Building Blocks ◽  
Cellular Processes ◽  
Pathological Conditions ◽  
Surrounding Environment ◽  
Selective Population ◽  
Different Types ◽  
Cytoplasmic Content

Although cells are a part of the whole organism, classical dogma emphasizes that individual cells function autonomously. Many physiological and pathological conditions, including cancer, and metabolic and neurodegenerative diseases, have been considered mechanistically as cell-autonomous pathologies, meaning those that damage or defect within a selective population of affected cells suffice to produce disease. It is becoming clear, however, that cells and cellular processes cannot be considered in isolation. Best known for shuttling cytoplasmic content to the lysosome for degradation and repurposing of recycled building blocks such as amino acids, nucleotides, and fatty acids, autophagy serves a housekeeping function in every cell and plays key roles in cell development, immunity, tissue remodeling, and homeostasis with the surrounding environment and the distant organs. In this review, we underscore the importance of taking interactions with the microenvironment into consideration while addressing the cell autonomous and non-autonomous functions of autophagy between cells of the same and different types and in physiological and pathophysiological situations.

scholarly journals PPARγ and Cognitive Performance

2019 ◽  
Vol 20 (20) ◽  
pp. 5068 ◽  
Author(s):  
Michele d’Angelo ◽  
Vanessa Castelli ◽  
Mariano Catanesi ◽  
Andrea Antonosante ◽  
Reyes Dominguez-Benot ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Neurodegenerative Diseases ◽  
Signaling Pathways ◽  
Neurite Outgrowth ◽  
Cognitive Performance ◽  
Nuclear Receptors ◽  
Neuroprotective Agents ◽  
Pathological Conditions ◽  
Pparγ Agonists ◽  
Mental Decline

Recent findings have led to the discovery of many signaling pathways that link nuclear receptors with human conditions, including mental decline and neurodegenerative diseases. PPARγ agonists have been indicated as neuroprotective agents, supporting synaptic plasticity and neurite outgrowth. For these reasons, many PPARγ ligands have been proposed for the improvement of cognitive performance in different pathological conditions. In this review, the research on this issue is extensively discussed.

scholarly journals Friends or Foes: Matrix Metalloproteinases and Their Multifaceted Roles in Neurodegenerative Diseases

2015 ◽  
Vol 2015 ◽  
pp. 1-27 ◽  
Author(s):  
Marjana Brkic ◽  
Sriram Balusu ◽  
Claude Libert ◽  
Roosmarijn E. Vandenbroucke
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Matrix Metalloproteinases ◽  
Neurodegenerative Diseases ◽  
Therapeutic Strategy ◽  
Pathological Conditions ◽  
Progressive Loss ◽  
Neuro Inflammation ◽  
Potential Use ◽  
Lateral Sclerosis

Neurodegeneration is a chronic progressive loss of neuronal cells leading to deterioration of central nervous system (CNS) functionality. It has been shown that neuroinflammation precedes neurodegeneration in various neurodegenerative diseases. Matrix metalloproteinases (MMPs), a protein family of zinc-containing endopeptidases, are essential in (neuro)inflammation and might be involved in neurodegeneration. Although MMPs are indispensable for physiological development and functioning of the organism, they are often referred to as double-edged swords due to their ability to also inflict substantial damage in various pathological conditions. MMP activity is strictly controlled, and its dysregulation leads to a variety of pathologies. Investigation of their potential use as therapeutic targets requires a better understanding of their contributions to the development of neurodegenerative diseases. Here, we review MMPs and their roles in neurodegenerative diseases: Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), Huntington’s disease (HD), and multiple sclerosis (MS). We also discuss MMP inhibition as a possible therapeutic strategy to treat neurodegenerative diseases.

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