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.

scholarly journals Paraoxonase Role in Human Neurodegenerative Diseases

Antioxidants ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 11
Author(s):  
Cadiele Oliana Reichert ◽  
Debora Levy ◽  
Sergio P. Bydlowski
Keyword(s):  
Oxidative Stress ◽  
Multiple Sclerosis ◽  
Amyotrophic Lateral Sclerosis ◽  
Neurodegenerative Diseases ◽  
High Density Lipoprotein ◽  
Density Lipoprotein ◽  
Structural Homology ◽  
Redox Systems ◽  
Genetic Cluster ◽  
Lateral Sclerosis

The human body has biological redox systems capable of preventing or mitigating the damage caused by increased oxidative stress throughout life. One of them are the paraoxonase (PON) enzymes. The PONs genetic cluster is made up of three members (PON1, PON2, PON3) that share a structural homology, located adjacent to chromosome seven. The most studied enzyme is PON1, which is associated with high density lipoprotein (HDL), having paraoxonase, arylesterase and lactonase activities. Due to these characteristics, the enzyme PON1 has been associated with the development of neurodegenerative diseases. Here we update the knowledge about the association of PON enzymes and their polymorphisms and the development of multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), Alzheimer’s disease (AD) and Parkinson’s disease (PD).

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 Advances of Zebrafish in Neurodegenerative Disease: From Models to Drug Discovery

2021 ◽  
Vol 12 ◽  
Author(s):  
Xiaobo Wang ◽  
Jin-Bao Zhang ◽  
Kai-Jie He ◽  
Fen Wang ◽  
Chun-Feng Liu
Keyword(s):  
Drug Discovery ◽  
Neurodegenerative Disease ◽  
Danio Rerio ◽  
New Technologies ◽  
Pathological Conditions ◽  
Disease Modifying Therapies ◽  
Progressive Loss ◽  
Pharmacological Targets ◽  
Lateral Sclerosis

Neurodegenerative disease (NDD), including Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis, are characterized by the progressive loss of neurons which leads to the decline of motor and/or cognitive function. Currently, the prevalence of NDD is rapidly increasing in the aging population. However, valid drugs or treatment for NDD are still lacking. The clinical heterogeneity and complex pathogenesis of NDD pose a great challenge for the development of disease-modifying therapies. Numerous animal models have been generated to mimic the pathological conditions of these diseases for drug discovery. Among them, zebrafish (Danio rerio) models are progressively emerging and becoming a powerful tool for in vivo study of NDD. Extensive use of zebrafish in pharmacology research or drug screening is due to the high conserved evolution and 87% homology to humans. In this review, we summarize the zebrafish models used in NDD studies, and highlight the recent findings on pharmacological targets for NDD treatment. As high-throughput platforms in zebrafish research have rapidly developed in recent years, we also discuss the application prospects of these new technologies in future NDD research.

scholarly journals Neuroinflammation in neurodegenerative disorders: the roles of microglia and astrocytes

2020 ◽  
Vol 9 (1) ◽  
Author(s):  
Hyuk Sung Kwon ◽  
Seong-Ho Koh
Keyword(s):  
Central Nervous System ◽  
Neurodegenerative Diseases ◽  
Neurodegenerative Disorders ◽  
Inflammatory Responses ◽  
Therapeutic Drugs ◽  
M1 Phenotype ◽  
The Central Nervous System ◽  
The Relationship ◽  
Lateral Sclerosis ◽  
M2 Phenotype

AbstractNeuroinflammation is associated with neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis. Microglia and astrocytes are key regulators of inflammatory responses in the central nervous system. The activation of microglia and astrocytes is heterogeneous and traditionally categorized as neurotoxic (M1-phenotype microglia and A1-phenotype astrocytes) or neuroprotective (M2-phenotype microglia and A2-phenotype astrocytes). However, this dichotomized classification may not reflect the various phenotypes of microglia and astrocytes. The relationship between these activated glial cells is also very complicated, and the phenotypic distribution can change, based on the progression of neurodegenerative diseases. A better understanding of the roles of microglia and astrocytes in neurodegenerative diseases is essential for developing effective therapies. In this review, we discuss the roles of inflammatory response in neurodegenerative diseases, focusing on the contributions of microglia and astrocytes and their relationship. In addition, we discuss biomarkers to measure neuroinflammation and studies on therapeutic drugs that can modulate neuroinflammation.

scholarly journals Immune Responses in Neurodegenerative Diseases

2015 ◽  
Vol 12 (1) ◽  
pp. 67-76 ◽  
Author(s):  
R Shrestha ◽  
Shakya Shrestha ◽  
O Millington ◽  
J Brewer ◽  
T Bushell
Keyword(s):  
Multiple Sclerosis ◽  
Immune Responses ◽  
Neurodegenerative Diseases ◽  
Immune Cells ◽  
Review Article ◽  
Progressive Loss ◽  
Parkinson’S Diseases ◽  
Key Factor ◽  
Huge Impact ◽  
Diseased Condition

Neurodegenerative disease is a progressive loss of neurons from central nervous system and has a huge impact on health care system. Various causes have been proposed of which inflammation has been suggested to be a probable key factor in the most of such conditions. The involvement of immune cells including lymphocytes in such diseased condition of the CNS supports this notion. The effective therapy for these diseases has been sought for more than a half century but still lacking such therapy. On such basis this review article has mainly focussed on evidence of the involvement of immune cells in various neurodegenerative diseases including Alzheimer’s disease, Parkinson’s diseases and Multiple sclerosis and suggests a possible therapy of such diseased conditions of the CNS by the modulation of immune system.Kathmandu University Medical Journal Vol.12(1) 2014: 67-76

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

2020 ◽  
Vol 26 (21) ◽  
pp. 2475-2491 ◽  
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.

Phosphodiesterase inhibitors suppress IL-12 production with microglia and T helper 1 development

2003 ◽  
Vol 9 (6) ◽  
pp. 574-578 ◽  
Author(s):  
Akio Suzumura ◽  
Atsushi Ito ◽  
Tetsuya Mizuno
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Nervous System ◽  
Therapeutic Strategy ◽  
Phosphodiesterase Inhibitors ◽  
T Helper ◽  
T Helper 1 ◽  
Chain Reaction ◽  
The Central Nervous System ◽  
Antigen Presenting

The effects of phosphodiesterase inhibitors (PDEIs) on interleukin (IL)-12 production by microglia, antigen-presenting cells in the central nervous system (C NS), were examined to learn how they affect T cell differentiatio n in the C NS. PDEIs significantly suppressed the microglial IL-12 production, as determined by reverse transcriptase-po lymerase chain reaction for IL-12 p35 and p40 mRNA expression and by an ELISA specific for IL-12 functional hetero dimer, p70. In addition, the PDEI ibudilast also suppressed interferon-g, but not IL-4 or IL-10, production by myelin oligodendro cyte glycoprotein (MO G)-specific T cells reactivated with MO G in the presence of microglia. Thus, PDEIs may also suppress differentiatio n of T helper 1 (Th1) in the C NS. PDEIs can be of use for future therapeutic strategy to treat Th1-mediated diseases, such as multiple sclerosis.

scholarly journals Acid-Sensing Ion Channels as Potential Therapeutic Targets in Neurodegeneration and Neuroinflammation

2017 ◽  
Vol 2017 ◽  
pp. 1-18 ◽  
Author(s):  
Audrey Ortega-Ramírez ◽  
Rosario Vega ◽  
Enrique Soto
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Nervous System ◽  
Ion Channels ◽  
Neurodegenerative Diseases ◽  
Therapeutic Targets ◽  
Recent Advances ◽  
Acid Sensing Ion Channels ◽  
Inflammatory Processes

Acid-sensing ion channels (ASICs) are a family of proton-sensing channels that are voltage insensitive, cation selective (mostly permeable to Na+), and nonspecifically blocked by amiloride. Derived from 5 genes (ACCN1–5), 7 subunits have been identified, 1a, 1b, 2a, 2b, 3, 4, and 5, that are widely expressed in the peripheral and central nervous system as well as other tissues. Over the years, different studies have shown that activation of these channels is linked to various physiological and pathological processes, such as memory, learning, fear, anxiety, ischemia, and multiple sclerosis to name a few, so their potential as therapeutic targets is increasing. This review focuses on recent advances that have helped us to better understand the role played by ASICs in different pathologies related to neurodegenerative diseases, inflammatory processes, and pain.

scholarly journals The Role of Microglia in the Development of Neurodegenerative Diseases

Biomedicines ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1449
Author(s):  
Jae-Won Lee ◽  
Wanjoo Chun ◽  
Hee Jae Lee ◽  
Seong-Man Kim ◽  
Jae-Hong Min ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Neurodegenerative Diseases ◽  
Microglial Activation ◽  
Therapeutic Strategy ◽  
Experimental Animal Models ◽  
Effective Therapeutic Strategy ◽  
The Central Nervous System ◽  
Animal Models Of Epilepsy ◽  
Models Of Epilepsy

Microglia play an important role in the maintenance and neuroprotection of the central nervous system (CNS) by removing pathogens, damaged neurons, and plaques. Recent observations emphasize that the promotion and development of neurodegenerative diseases (NDs) are closely related to microglial activation. In this review, we summarize the contribution of microglial activation and its associated mechanisms in NDs, such as epilepsy, Alzheimer’s disease (AD), Parkinson’s disease (PD), and Huntington’s disease (HD), based on recent observations. This review also briefly introduces experimental animal models of epilepsy, AD, PD, and HD. Thus, this review provides a better understanding of microglial functions in the development of NDs, suggesting that microglial targeting could be an effective therapeutic strategy for these diseases.

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