scholarly journals From peroxisomal disorders to common neurodegenerative diseases – the role of ether phospholipids in the nervous system

FEBS Letters ◽  
2017 ◽  
Vol 591 (18) ◽  
pp. 2761-2788 ◽  
Author(s):  
Fabian Dorninger ◽  
Sonja Forss‐Petter ◽  
Johannes Berger
Keyword(s):  
Nervous System ◽  
Neurodegenerative Diseases ◽  
Peroxisomal Disorders ◽  
Ether Phospholipids

scholarly journals Proteinopathies and OXPHOS dysfunction in neurodegenerative diseases

2017 ◽  
Vol 216 (12) ◽  
pp. 3917-3929 ◽  
Author(s):  
Hibiki Kawamata ◽  
Giovanni Manfredi
Keyword(s):  
Nervous System ◽  
Oxidative Phosphorylation ◽  
Neurodegenerative Diseases ◽  
Gene Mutations ◽  
Misfolded Proteins ◽  
Protein Homeostasis ◽  
Abnormal Protein ◽  
Oxidative Phosphorylation System ◽  
Intermediate Metabolism

Mitochondria participate in essential processes in the nervous system such as energy and intermediate metabolism, calcium homeostasis, and apoptosis. Major neurodegenerative diseases are characterized pathologically by accumulation of misfolded proteins as a result of gene mutations or abnormal protein homeostasis. Misfolded proteins associate with mitochondria, forming oligomeric and fibrillary aggregates. As mitochondrial dysfunction, particularly of the oxidative phosphorylation system (OXPHOS), occurs in neurodegeneration, it is postulated that such defects are caused by the accumulation of misfolded proteins. However, this hypothesis and the pathological role of proteinopathies in mitochondria remain elusive. In this study, we critically review the proposed mechanisms whereby exemplary misfolded proteins associate with mitochondria and their consequences on OXPHOS.

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 The Role of Metals in Neurodegenerative Diseases of the Central Nervous System

2020 ◽  
Vol 8 (2) ◽  
pp. 130-146
Author(s):  
Afshin Montazeri ◽  
Milad Akhlaghi ◽  
Ahmad Reza Barahimi ◽  
Ali Jahanbazi Jahan Abad ◽  
Reza Jabbari ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Neurodegenerative Diseases ◽  
The Central Nervous System

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 Primary Cilia Structure Is Prolonged in Enteric Neurons of 5xFAD Alzheimer’s Disease Model Mice

2021 ◽  
Vol 22 (24) ◽  
pp. 13564
Author(s):  
Vu Thu Thuy Nguyen ◽  
Lena Brücker ◽  
Ann-Kathrin Volz ◽  
Julia C. Baumgärtner ◽  
Malena dos Santos Guilherme ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Nervous System ◽  
Neurodegenerative Diseases ◽  
Enteric Nervous System ◽  
Primary Cilium ◽  
Primary Cilia ◽  
Enteric Neurons ◽  
Wild Type ◽  
5Xfad Mice

Neurodegenerative diseases such as Alzheimer’s disease (AD) have long been acknowledged as mere disorders of the central nervous system (CNS). However, in recent years the gut with its autonomous nervous system and the multitude of microbial commensals has come into focus. Changes in gut properties have been described in patients and animal disease models such as altered enzyme secretion or architecture of the enteric nervous system. The underlying cellular mechanisms have so far only been poorly investigated. An important organelle for integrating potentially toxic signals such as the AD characteristic A-beta peptide is the primary cilium. This microtubule-based signaling organelle regulates numerous cellular processes. Even though the role of primary cilia in a variety of developmental and disease processes has recently been recognized, the contribution of defective ciliary signaling to neurodegenerative diseases such as AD, however, has not been investigated in detail so far. The AD mouse model 5xFAD was used to analyze possible changes in gut functionality by organ bath measurement of peristalsis movement. Subsequently, we cultured primary enteric neurons from mutant mice and wild type littermate controls and assessed for cellular pathomechanisms. Neurite mass was quantified within transwell culturing experiments. Using a combination of different markers for the primary cilium, cilia number and length were determined using fluorescence microscopy. 5xFAD mice showed altered gut anatomy, motility, and neurite mass of enteric neurons. Moreover, primary cilia could be demonstrated on the surface of enteric neurons and exhibited an elongated phenotype in 5xFAD mice. In parallel, we observed reduced β-Catenin expression, a key signaling molecule that regulates Wnt signaling, which is regulated in part via ciliary associated mechanisms. Both results could be recapitulated via in vitro treatments of enteric neurons from wild type mice with A-beta. So far, only a few reports on the probable role of primary cilia in AD can be found. Here, we reveal for the first time an architectural altered phenotype of primary cilia in the enteric nervous system of AD model mice, elicited potentially by neurotoxic A-beta. Potential changes on the sub-organelle level—also in CNS-derived neurons—require further investigations.

scholarly journals Metallothionein in Brain Disorders

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Daniel Juárez-Rebollar ◽  
Camilo Rios ◽  
Concepción Nava-Ruíz ◽  
Marisela Méndez-Armenta
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Neurodegenerative Diseases ◽  
Neurological Disorders ◽  
Regulation Of Gene Expression ◽  
Main Function ◽  
Brain Disorders ◽  
Essential Metals ◽  
The Central Nervous System

Metallothioneins are a family of proteins which are able to bind metals intracellularly, so their main function is to regulate the cellular metabolism of essential metals. There are 4 major isoforms of MTs (I–IV), three of which have been localized in the central nervous system. MT-I and MT-II have been localized in the spinal cord and brain, mainly in astrocytes, whereas MT-III has been found mainly in neurons. MT-I and MT-II have been considered polyvalent proteins whose main function is to maintain cellular homeostasis of essential metals such as zinc and copper, but other functions have also been considered: detoxification of heavy metals, regulation of gene expression, processes of inflammation, and protection against free radicals generated by oxidative stress. On the other hand, the MT-III has been related in events of pathogenesis of neurodegenerative diseases such as Parkinson and Alzheimer. Likewise, the participation of MTs in other neurological disorders has also been reported. This review shows recent evidence about the role of MT in the central nervous system and its possible role in neurodegenerative diseases as well as in brain disorders.

scholarly journals Role of Connexins 30, 36, and 43 in Brain Tumors, Neurodegenerative Diseases, and Neuroprotection

Cells ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 846 ◽  
Author(s):  
Oscar F. Sánchez ◽  
Andrea V. Rodríguez ◽  
José M. Velasco-España ◽  
Laura C. Murillo ◽  
Jhon-Jairo Sutachan ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Neurodegenerative Diseases ◽  
Posttranslational Modifications ◽  
Cell Communication ◽  
Normal Function ◽  
Epigenetic Mechanisms ◽  
Communication Processes ◽  
The Central Nervous System

Gap junction (GJ) channels and their connexins (Cxs) are complex proteins that have essential functions in cell communication processes in the central nervous system (CNS). Neurons, astrocytes, oligodendrocytes, and microglial cells express an extraordinary repertory of Cxs that are important for cell to cell communication and diffusion of metabolites, ions, neurotransmitters, and gliotransmitters. GJs and Cxs not only contribute to the normal function of the CNS but also the pathological progress of several diseases, such as cancer and neurodegenerative diseases. Besides, they have important roles in mediating neuroprotection by internal or external molecules. However, regulation of Cx expression by epigenetic mechanisms has not been fully elucidated. In this review, we provide an overview of the known mechanisms that regulate the expression of the most abundant Cxs in the central nervous system, Cx30, Cx36, and Cx43, and their role in brain cancer, CNS disorders, and neuroprotection. Initially, we focus on describing the Cx gene structure and how this is regulated by epigenetic mechanisms. Then, the posttranslational modifications that mediate the activity and stability of Cxs are reviewed. Finally, the role of GJs and Cxs in glioblastoma, Alzheimer’s, Parkinson’s, and Huntington’s diseases, and neuroprotection are analyzed with the aim of shedding light in the possibility of using Cx regulators as potential therapeutic molecules.

scholarly journals Relationship between Zinc (Zn2+) and Glutamate Receptors in the Processes Underlying Neurodegeneration

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Bartłomiej Pochwat ◽  
Gabriel Nowak ◽  
Bernadeta Szewczyk
Keyword(s):  
Nervous System ◽  
Neurodegenerative Diseases ◽  
Efficient Control ◽  
Brain Circuit ◽  
The One ◽  
Clinical Conditions ◽  
The Relationship ◽  
Glutamate System ◽  
Regulative Function

The results from numerous studies have shown that an imbalance between particular neurotransmitters may lead to brain circuit dysfunction and development of many pathological states. The significance of glutamate pathways for the functioning of the nervous system is equivocal. On the one hand, glutamate transmission is necessary for neuroplasticity, synaptogenesis, or cell survival, but on the other hand an excessive and long-lasting increased level of glutamate in the synapse may lead to cell death. Under clinical conditions, hyperactivity of the glutamate system is associated with ischemia, epilepsy, and neurodegenerative diseases such as Alzheimer’s, Huntington’s, and many others. The achievement of glutamate activity in the physiological range requires efficient control by endogenous regulatory factors. Due to the fact that the free pool of ion Zn2+is a cotransmitter in some glutamate neurons; the role of this element in the pathophysiology of a neurodegenerative diseases has been intensively studied. There is a lot of evidence for Zn2+dyshomeostasis and glutamate system abnormalities in ischemic and neurodegenerative disorders. However, the precise interaction between Zn2+regulative function and the glutamate system is still not fully understood. This review describes the relationship between Zn2+and glutamate dependent signaling pathways under selected pathological central nervous system (CNS) conditions.

scholarly journals Microbial Infections Are a Risk Factor for Neurodegenerative Diseases

2021 ◽  
Vol 15 ◽  
Author(s):  
Sarah K. Lotz ◽  
Britanie M. Blackhurst ◽  
Katie L. Reagin ◽  
Kristen E. Funk
Keyword(s):  
Nervous System ◽  
Neurodegenerative Diseases ◽  
Immune Cells ◽  
Disease Process ◽  
Cellular Mechanisms ◽  
Microbial Infections ◽  
The Central Nervous System ◽  
Nervous System Function ◽  
Peripheral Immune Cells

Neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis, comprise a family of disorders characterized by progressive loss of nervous system function. Neuroinflammation is increasingly recognized to be associated with many neurodegenerative diseases but whether it is a cause or consequence of the disease process is unclear. Of growing interest is the role of microbial infections in inciting degenerative neuroinflammatory responses and genetic factors that may regulate those responses. Microbial infections cause inflammation within the central nervous system through activation of brain-resident immune cells and infiltration of peripheral immune cells. These responses are necessary to protect the brain from lethal infections but may also induce neuropathological changes that lead to neurodegeneration. This review discusses the molecular and cellular mechanisms through which microbial infections may increase susceptibility to neurodegenerative diseases. Elucidating these mechanisms is critical for developing targeted therapeutic approaches that prevent the onset and slow the progression of neurodegenerative diseases.

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