Neurodegenerative Disorders Progression

2019 ◽  
pp. 129-152
Author(s):  
Ramneek Kaur ◽  
Harleen Kaur ◽  
Rashi Rajput ◽  
Sachin Kumar ◽  
Rachana R. ◽  
...  
Keyword(s):  
Neurodegenerative Disorders ◽  
Neural Systems ◽  
Diverse Group ◽  
Key Factors ◽  
Neuron Death ◽  
Postsynaptic Activity ◽  
Neural Transmission ◽  
The Central Nervous System ◽  
Neural Signaling ◽  
Lateral Sclerosis

Neurodegenerative disorders (NDs) are a diverse group of disorders characterized by selective and progressive loss of neural systems that cause dysfunction of the central nervous system (CNS). The examples of NDs include Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), and Huntington's disease (HD). The aggregated proteins block or disrupt the normal proteosomal turnover, autophagy, and become abnormally modified with time, generating toxicity via pathways thereby resulting in neurodegeneration and neuron death. The chapter highlights the understanding in the areas of AD, PD, HD as illustrative of major research so as to define the key factors and events in the improvement of NDs. It defines the physiological functioning of neural transmission (presynaptic, postsynaptic activity) at neural signaling pathway, then the dynamics of neuronal dysfunctioning and its molecular mechanism. Further, it also discusses the progression from synaptic dysfunction to transmission failure followed by NDs.

Healthy Gut, Healthy Brain: The Gut Microbiome in Neurodegenerative Disorders

2020 ◽  
Vol 20 (13) ◽  
pp. 1142-1153 ◽  
Author(s):  
Sreyashi Chandra ◽  
Md. Tanjim Alam ◽  
Jhilik Dey ◽  
Baby C. Pulikkaparambil Sasidharan ◽  
Upasana Ray ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Neurodegenerative Disorders ◽  
The Body ◽  
Therapeutic Approaches ◽  
Cns Disorders ◽  
Physiological Conditions ◽  
Pathological Conditions ◽  
The Central Nervous System ◽  
Present Understanding ◽  
Lateral Sclerosis

Background: The central nervous system (CNS) known to regulate the physiological conditions of human body, also itself gets dynamically regulated by both the physiological as well as pathological conditions of the body. These conditions get changed quite often, and often involve changes introduced into the gut microbiota which, as studies are revealing, directly modulate the CNS via a crosstalk. This cross-talk between the gut microbiota and CNS, i.e., the gut-brain axis (GBA), plays a major role in the pathogenesis of many neurodegenerative disorders such as Parkinson’s disease (PD), Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS) and Huntington’s disease (HD). Objective: We aim to discuss how gut microbiota, through GBA, regulate neurodegenerative disorders such as PD, AD, ALS, MS and HD. Methods: In this review, we have discussed the present understanding of the role played by the gut microbiota in neurodegenerative disorders and emphasized the probable therapeutic approaches being explored to treat them. Results: In the first part, we introduce the GBA and its relevance, followed by the changes occurring in the GBA during neurodegenerative disorders and then further discuss its role in the pathogenesis of these diseases. Finally, we discuss its applications in possible therapeutics of these diseases and the current research improvements being made to better investigate this interaction. Conclusion: We concluded that alterations in the intestinal microbiota modulate various activities that could potentially lead to CNS disorders through interactions via the GBA.

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 Partial Failure of Proteostasis Systems Counteracting TDP-43 Aggregates in Neurodegenerative Diseases

2019 ◽  
Vol 20 (15) ◽  
pp. 3685 ◽  
Author(s):  
Roberta Cascella ◽  
Giulia Fani ◽  
Alessandra Bigi ◽  
Fabrizio Chiti ◽  
Cristina Cecchi
Keyword(s):  
Neurodegenerative Disorders ◽  
Frontotemporal Lobar Degeneration ◽  
Strong Influence ◽  
Genetic Mutations ◽  
Oxygen Species ◽  
Caspase Activation ◽  
Post Translational Modifications ◽  
Key Factor ◽  
The Central Nervous System ◽  
Lateral Sclerosis

Frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS) are progressive and fatal neurodegenerative disorders showing mislocalization and cytosolic accumulation of TDP-43 inclusions in the central nervous system. The decrease in the efficiency of the clearance systems in aging, as well as the presence of genetic mutations of proteins associated with cellular proteostasis in the familial forms of TDP-43 proteinopathies, suggest that a failure of these protein degradation systems is a key factor in the aetiology of TDP-43 associated disorders. Here we show that the internalization of human pre-formed TDP-43 aggregates in the murine neuroblastoma N2a cells promptly resulted in their ubiquitination and hyperphosphorylation by endogenous machineries, mimicking the post-translational modifications observed in patients. Moreover, our data identify mitochondria as the main responsible sites for the alteration of calcium homeostasis induced by TDP-43 aggregates, which, in turn, stimulates an increase in reactive oxygen species and, finally, caspase activation. The inhibition of TDP-43 proteostasis in the presence of selective inhibitors against the proteasome and macroautophagy systems revealed that these two systems are both severely involved in TDP-43 accumulation and have a strong influence on each other in neurodegenerative disorders associated with TDP-43.

scholarly journals The Microbiota-Gut-Brain Axis as a Key to Neuropsychiatric Disorders: A Mini Review

2021 ◽  
Vol 10 (20) ◽  
pp. 4640
Author(s):  
Katarzyna Stopińska ◽  
Maria Radziwoń-Zaleska ◽  
Izabela Domitrz
Keyword(s):  
Nervous System ◽  
Neurodegenerative Disorders ◽  
Essential Role ◽  
Short Chain Fatty Acids ◽  
Autism Spectrum ◽  
Gut Flora ◽  
Neuropsychological Disorders ◽  
The Central Nervous System ◽  
Gut Microorganisms ◽  
Lateral Sclerosis

The central nervous system (CNS) is closely related to the gastrointestinal tract, mainly through regulating its function and homeostasis. Simultaneously, the gut flora affects the CNS and plays an essential role in the pathogenesis of neurologic and neuropsychological disorders such as Parkinson’s and Alzheimer’s disease, multiple sclerosis, amyotrophic lateral sclerosis or autism spectrum disorder. The population of gut microorganisms contains more than one billion bacteria. The most common are six phyla: Proteobacteria, Actinomyces, Verucomicrobia, Fusobacteria, and dominant Bacteroides with Firmicutes. The microbiota–gut–brain axis is a bidirectional nervous, endocrine, and immune communication between these two organs. They are connected through a variety of pathways, including the vagus nerve, the immune system, microbial metabolites such as short-chain fatty acids (SCFAs), the enteric nervous system, and hormones. Age, diet, antibiotics influence the balance of gut microorganisms and probably lead to the development of neurodegenerative disorders. In this article, a review is presented and discussed, with a specific focus on the changes of gut microbiota, gut–brain axis, related disorders, and the factors that influence gut imbalance.

Role of Prostaglandins in Multiple Sclerosis

2020 ◽  
Vol 26 (7) ◽  
pp. 730-742
Author(s):  
Surendra Gulla ◽  
Dakshayani Lomada ◽  
Anusha Lade ◽  
Reddanna Pallu ◽  
Madhava C. Reddy
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Nervous System ◽  
Neurodegenerative Disorders ◽  
Cognitive Disability ◽  
Demyelinating Disorder ◽  
Mediators Of Inflammation ◽  
The Central Nervous System ◽  
Lateral Sclerosis

: Multiple sclerosis (MS) is an autoimmune demyelinating disorder with chronic inflammation in the central nervous system, manifested by both physical and cognitive disability. Neuroinflammation and neurodegeneration are the phenomena that appear in the central nervous system associated with various neurodegenerative disorders, including MS, Alzheimer’s diseases, amyotrophic lateral sclerosis and Parkinson’s disease. Prostaglandins are one of the major mediators of inflammation that exhibit an important function in enhancing neuroinflammatory and neurodegenerative processes. These mediators would help understand the pathophysiology of MS as the combination of antagonists or agonists of prostaglandins receptors could be beneficial during the treatment of MS. The present review focuses on the role played by different prostaglandins and the enzymes which produced them in the etiopathogenesis of MS.

scholarly journals Amyotrophic Lateral Sclerosis (ALS): Stressed by Dysfunctional Mitochondria-Endoplasmic Reticulum Contacts (MERCs)

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1789
Author(s):  
Junsheng Chen ◽  
Arthur Bassot ◽  
Fabrizio Giuliani ◽  
Thomas Simmen
Keyword(s):  
Oxidative Stress ◽  
Endoplasmic Reticulum ◽  
Amyotrophic Lateral Sclerosis ◽  
Energy Output ◽  
Central Position ◽  
Neuron Death ◽  
Mutant Proteins ◽  
The Central Nervous System ◽  
Metabolic Output ◽  
Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease for which there is currently no cure. Progress in the characterization of other neurodegenerative mechanisms has shifted the spotlight onto an intracellular structure called mitochondria-endoplasmic reticulum (ER) contacts (MERCs) whose ER portion can be biochemically isolated as mitochondria-associated membranes (MAMs). Within the central nervous system (CNS), these structures control the metabolic output of mitochondria and keep sources of oxidative stress in check via autophagy. The most relevant MERC controllers in the ALS pathogenesis are vesicle-associated membrane protein-associated protein B (VAPB), a mitochondria-ER tether, and the ubiquitin-specific chaperone valosin containing protein (VCP). These two systems cooperate to maintain mitochondrial energy output and prevent oxidative stress. In ALS, mutant VAPB and VCP take a central position in the pathology through MERC dysfunction that ultimately alters or compromises mitochondrial bioenergetics. Intriguingly, both proteins are targets themselves of other ALS mutant proteins, including C9orf72, FUS, or TDP-43. Thus, a new picture emerges, where different triggers cause MERC dysfunction in ALS, subsequently leading to well-known pathological changes including endoplasmic reticulum (ER) stress, inflammation, and motor neuron death.

scholarly journals Peripheral biomarkers of oxidative stress in aging and Alzheimer's disease

2008 ◽  
Vol 2 (1) ◽  
pp. 2-8 ◽  
Author(s):  
Tania Marcourakis ◽  
Rosana Camarini ◽  
Elisa Mitiko Kawamoto ◽  
Leandro Rodrigues Scorsi ◽  
Cristoforo Scavone
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Disorders ◽  
Stress Markers ◽  
Markers Of Oxidative Stress ◽  
The Central Nervous System ◽  
Peripheral Markers ◽  
Lateral Sclerosis ◽  
Biomarkers Of Oxidative Stress

Abstract Aging is associated with a greatly increased incidence of a number of neurodegenerative disorders, including Alzheimer's disease (AD), Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS). These conditions are associated with chronic inflammation, which generates oxygen reactive species, ultimately responsible for a process known as oxidative stress. It is well established that this process is the culprit of neurodegeneration, and there are also mounting evidences that it is not restricted to the central nervous system. Indeed, several studies, including some by our group, have demonstrated that increased peripheral oxidative stress markers are associated to aging and, more specifically, to AD. Therefore, it is very instigating to regard aging and AD as systemic conditions that might be determined by studying peripheral markers of oxidative stress.

scholarly journals Regulation of Brain Cholesterol: What Role Do Liver X Receptors Play in Neurodegenerative Diseases?

2019 ◽  
Vol 20 (16) ◽  
pp. 3858 ◽  
Author(s):  
Kevin Mouzat ◽  
Aleksandra Chudinova ◽  
Anne Polge ◽  
Jovana Kantar ◽  
William Camu ◽  
...  
Keyword(s):  
Neurodegenerative Disorders ◽  
Target Genes ◽  
Major Constituent ◽  
Liver X Receptors ◽  
Neuroprotective Effects ◽  
Brain Cholesterol ◽  
Pharmacological Targets ◽  
The Central Nervous System ◽  
X Receptors ◽  
Lateral Sclerosis

Liver X Receptors (LXR) alpha and beta are two members of nuclear receptor superfamily documented as endogenous cholesterol sensors. Following conversion of cholesterol in oxysterol, both LXR isoforms detect intracellular concentrations and act as transcription factors to promote expression of target genes. Among their numerous physiological roles, they act as central cholesterol-lowering factors. In the central nervous system (CNS), cholesterol has been shown to be an essential determinant of brain function, particularly as a major constituent of myelin and membranes. In the brain, LXRs act as cholesterol central regulators, and, beyond this metabolic function, LXRs have additional roles such as providing neuroprotective effects and lowering neuroinflammation. In many neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS), Alzheimer’s disease (AD), and multiple sclerosis (MS), dysregulations of cholesterol and oxysterol have been reported. In this paper, we propose to focus on recent advances in the knowledge of the LXRs roles on brain cholesterol and oxysterol homeostasis, neuroinflammation, neuroprotection, and their putative involvement in neurodegenerative disorders. We will discuss their potential use as candidates for both molecular diagnosis and as promising pharmacological targets in the treatment of ALS, AD, or MS patients.

scholarly journals Acylated Ghrelin is Protective Against 6-OHDA-induced Neurotoxicity by Regulating Autophagic Flux

2021 ◽  
Vol 11 ◽  
Author(s):  
Xin He ◽  
Wei Yuan ◽  
Fei Liu ◽  
Juan Feng ◽  
Yanxia Guo
Keyword(s):  
Neurodegenerative Disorders ◽  
Caspase 3 ◽  
Cell Model ◽  
Autophagic Flux ◽  
Acylated Ghrelin ◽  
Neuron Death ◽  
Upstream Regulator ◽  
The Central Nervous System ◽  
And Function ◽  
Related Proteins

Parkinson’s disease (PD) is one of the most common neurodegenerative disorders, and our previous study revealed that autophagic flux dysfunction contributes to the neuron death in 6-OHDA-induced PD models. Acylated ghrelin is a neuropeptide that has a variety of actions in the central nervous system. In the current study, we aimed to investigate whether ghrelin is neuroprotective in 6-OHDA-induced rat model and SH-SY5Y cell model and whether it is related to autophagic flux regulation. We observed that ghrelin could effectively reduce apomorphine-induced contralateral rotation in 6-OHDA-induced PD rats, preserve the expression of tyrosine hydroxylase (TH) and increase the cell viability. It could upregulate the expression of autophagy related proteins like Atg7 and LC3-II and downregulate p62, and downregulate apoptosis related proteins like bax and cleaved caspase 3. SH-SY5Y cells transfected with adenovirus Ad-mCherry-GFP-LC3B further revealed that ghrelin could relieve the autophagic flux dysfunction induced by 6-OHDA. Lysotracker staining showed that ghrelin could reverse the decrease in lysosomes induced by 6-OHDA and immunofluorescence staining revealed a reverse of TFEB level in SH-SY5Y cells. Blocking autophagy activation with 3-methyladenine (3-MA) in rats treated with ghrelin and 6-OHDA showed no notable change in apoptosis-related markers, while blocking autophagosome fusion with lysosomes with chloroquine could notably reverse the downregulation of bax/bcl-2 ratio and cleaved caspase three expression by ghrelin. Additionally, knockdown ATG7, the upstream regulator of autophagy, with siRNA could further decrease the number of apoptotic cells in SH-SY5Y cells exposed to 6-OHDA and treated with ghrelin, while knockdown TFEB, a key transcription factor for lysosome biosynthesis and function, with siRNA could completely abolish the anti-apoptosis effect of ghrelin. These data suggest that ghrelin is neuroprotective in 6-OHDA-induced PD models via improving autophagic flux dysfunction and restoration of TFEB level.

Amyotrophic lateral sclerosis (ALS) and fronto-temporal dementia (FTD)

2020 ◽  
pp. 119-132
Author(s):  
Giancarlo Logroscino ◽  
Adriano Chiò
Keyword(s):  
Risk Factors ◽  
Central Nervous System ◽  
Amyotrophic Lateral Sclerosis ◽  
Neurodegenerative Disorders ◽  
Military Service ◽  
Motor System ◽  
Motor Pathways ◽  
Clinical Syndromes ◽  
The Central Nervous System ◽  
Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are both progressive neurodegenerative disorders considered part of the same spectrum of overlapping genetic neurological and clinical diseases. ALS involves primarily the motor system, but recent advances consider also the involvement of other parts of the central nervous system (CNS), primarily cognition. FTD presents clinical syndromes with behavioural and language variants, but some subtypes have motor involvement of the motor pathways and/or of some extrapyramidal areas. C9ORF72 is a gene responsible for 7–10% of cases both of sporadic and familial of ALS and FTD as well. Both ALS and FTD are rare diseases with incidence around 3/100,000 for ALS in Europe and FTD probably lower. The data for ALS have been mainly produced in Europe by a system of registries in limited territories. FTD data from populations are sparse. Trauma, smoking, military service, and agricultural occupation are environmental probable risk factors for ALS. No analytic data are available for FTD. FUS, TARDP, SOD 1, and C9ORF72 are the main genes involved in ALS, while C9ORF72, PGR, and TAU have been reported in FTD.

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