scholarly journals Systematic Review: Quantitative Susceptibility Mapping (QSM) of Brain Iron Profile in Neurodegenerative Diseases

2021 ◽  
Vol 15 ◽  
Author(s):  
Parsa Ravanfar ◽  
Samantha M. Loi ◽  
Warda T. Syeda ◽  
Tamsyn E. Van Rheenen ◽  
Ashley I. Bush ◽  
...  
Keyword(s):  
Systematic Review ◽  
Amyotrophic Lateral Sclerosis ◽  
Magnetic Susceptibility ◽  
Neurodegenerative Diseases ◽  
Huntington's Disease ◽  
Friedreich’S Ataxia ◽  
Susceptibility Mapping ◽  
Quantitative Susceptibility Mapping ◽  
The Brain ◽  
Lateral Sclerosis

Iron has been increasingly implicated in the pathology of neurodegenerative diseases. In the past decade, development of the new magnetic resonance imaging technique, quantitative susceptibility mapping (QSM), has enabled for the more comprehensive investigation of iron distribution in the brain. The aim of this systematic review was to provide a synthesis of the findings from existing QSM studies in neurodegenerative diseases. We identified 80 records by searching MEDLINE, Embase, Scopus, and PsycInfo databases. The disorders investigated in these studies included Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Wilson's disease, Huntington's disease, Friedreich's ataxia, spinocerebellar ataxia, Fabry disease, myotonic dystrophy, pantothenate-kinase-associated neurodegeneration, and mitochondrial membrane protein-associated neurodegeneration. As a general pattern, QSM revealed increased magnetic susceptibility (suggestive of increased iron content) in the brain regions associated with the pathology of each disorder, such as the amygdala and caudate nucleus in Alzheimer's disease, the substantia nigra in Parkinson's disease, motor cortex in amyotrophic lateral sclerosis, basal ganglia in Huntington's disease, and cerebellar dentate nucleus in Friedreich's ataxia. Furthermore, the increased magnetic susceptibility correlated with disease duration and severity of clinical features in some disorders. Although the number of studies is still limited in most of the neurodegenerative diseases, the existing evidence suggests that QSM can be a promising tool in the investigation of neurodegeneration.

scholarly journals Systematic review protocol: Quantitative susceptibility mapping of brain iron accumulation in neurodegenerative diseases

2020 ◽  
Author(s):  
Parsa Ravanfar ◽  
Samantha Loi ◽  
Tamsyn Van Rheenen ◽  
Ashley Bush ◽  
Patricia Desmond ◽  
...  
Keyword(s):  
Systematic Review ◽  
Neurodegenerative Diseases ◽  
Structural Changes ◽  
Susceptibility Mapping ◽  
Iron Deposition ◽  
Brain Iron ◽  
Systematic Review Protocol ◽  
Quantitative Susceptibility Mapping ◽  
Review Protocol ◽  
The Brain

AbstractIron has been found to play an important role in neurodegeneration. Quantitative susceptibility mapping (QSM) is a relatively new – and the most accurate - MRI technique available for assessment of iron deposition in the brain. There is a rapidly growing number of studies using QSM to investigate brain iron distribution in neurodegenerative diseases including but not limited to Alzheimer’s disease, Parkinson’s disease, Amyotrophic lateral sclerosis, Huntington disease and Wilson’s disease. These studies have shown increased iron deposition in the brain regions that are associated with the pathology of the disease. Additionally, QSM is found to be accurate in differential diagnosis of neurodegenerative diseases where clinical presentations are indistinguishable. Structural changes evidenced by QSM are reported to precede the onset of clinical manifestation of neurodegenerative diseases suggesting its benefit in early diagnosis. To our knowledge, no systematic review of QSM findings in neurodegenerative diseases has been published before. A systematic synthesis and conclusion of the existing evidence can improve our understanding of the pathophysiology of neurodegeneration, describe the clinical and research utility of QSM, and point out the direction for future studies in neuropsychiatric disorders.This document is a systematic review protocol developed in accordance with Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) guideline. This protocol is prepared as a guide for conducting a systematic review of studies investigating brain iron and microstructural changes in neurodegenerative diseases using quantitative susceptibility mapping (QSM). This protocol has also been submitted to Prospective Register of Systematic Reviews (PROSPERO) for registration. By publishing this protocol, we aim to enhance clarity and transparency of our systematic review and minimise the risk of bias in the process of its development.

scholarly journals Altered Blood-Brain Barrier and Blood-Spinal Cord Barrier Dynamics in Amyotrophic Lateral Sclerosis: Impact on Medication Efficacy and Safety

2021 ◽  
Author(s):  
Yijun Pan ◽  
Joseph Nicolazzo
Keyword(s):  
Spinal Cord ◽  
Amyotrophic Lateral Sclerosis ◽  
Neurodegenerative Diseases ◽  
Blood Brain Barrier ◽  
Large Body ◽  
Brain Barrier ◽  
Blood Brain ◽  
Blood Spinal Cord Barrier ◽  
The Brain ◽  
Lateral Sclerosis

The access of drugs into the central nervous system (CNS) is regulated by the blood-brain barrier (BBB) and blood-spinal cord barrier (BSCB). A large body of evidence supports perturbation of these barriers in neurodegenerative diseases, including Alzheimer’s disease and Parkinson’s disease. Modifications to the BBB and BSCB are also reported in amyotrophic lateral sclerosis (ALS), albeit these modifications have received less attention relative to those in other neurodegenerative diseases. Such alterations to the BBB and BSCB have the potential to impact on CNS exposure of drugs in ALS, modulating the effectiveness of drugs intended to reach the brain and the toxicity of drugs that are not intended to reach the brain. Given the clinical importance of these phenomena, this review will summarise reported modifications to the BBB and BSCB in ALS, discuss their impact on CNS drug exposure and suggest further research directions so as to optimise medicine use in people with ALS.

scholarly journals Common Factors in Neurodegeneration: A Meta-Study Revealing Shared Patterns on a Multi-Omics Scale

Cells ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 2642
Author(s):  
Nicolas Ruffini ◽  
Susanne Klingenberg ◽  
Susann Schweiger ◽  
Susanne Gerber
Keyword(s):  
Immune Response ◽  
Amyotrophic Lateral Sclerosis ◽  
Neurodegenerative Diseases ◽  
Huntington's Disease ◽  
Humoral Immune Response ◽  
Differentially Expressed ◽  
Humoral Immune ◽  
Proteomic Data ◽  
Go Terms ◽  
Lateral Sclerosis

Neurodegenerative diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), and amyotrophic lateral sclerosis (ALS) are heterogeneous, progressive diseases with frequently overlapping symptoms characterized by a loss of neurons. Studies have suggested relations between neurodegenerative diseases for many years (e.g., regarding the aggregation of toxic proteins or triggering endogenous cell death pathways). We gathered publicly available genomic, transcriptomic, and proteomic data from 177 studies and more than one million patients to detect shared genetic patterns between the neurodegenerative diseases on three analyzed omics-layers. The results show a remarkably high number of shared differentially expressed genes between the transcriptomic and proteomic levels for all conditions, while showing a significant relation between genomic and proteomic data between AD and PD and AD and ALS. We identified a set of 139 genes being differentially expressed in several transcriptomic experiments of all four diseases. These 139 genes showed overrepresented gene ontology (GO) Terms involved in the development of neurodegeneration, such as response to heat and hypoxia, positive regulation of cytokines and angiogenesis, and RNA catabolic process. Furthermore, the four analyzed neurodegenerative diseases (NDDs) were clustered by their mean direction of regulation throughout all transcriptomic studies for this set of 139 genes, with the closest relation regarding this common gene set seen between AD and HD. GO-Term and pathway analysis of the proteomic overlap led to biological processes (BPs), related to protein folding and humoral immune response. Taken together, we could confirm the existence of many relations between Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and amyotrophic lateral sclerosis on transcriptomic and proteomic levels by analyzing the pathways and GO-Terms arising in these intersections. The significance of the connection and the striking relation of the results to processes leading to neurodegeneration between the transcriptomic and proteomic data for all four analyzed neurodegenerative diseases showed that exploring many studies simultaneously, including multiple omics-layers of different neurodegenerative diseases simultaneously, holds new relevant insights that do not emerge from analyzing these data separately. Furthermore, the results shed light on processes like the humoral immune response that have previously been described only for certain diseases. Our data therefore suggest human patients with neurodegenerative diseases should be addressed as complex biological systems by integrating multiple underlying data sources.

Mitochondria and Neurodegeneration

2007 ◽  
Vol 27 (1-3) ◽  
pp. 87-104 ◽  
Author(s):  
Lucia Petrozzi ◽  
Giulia Ricci ◽  
Noemi J. Giglioli ◽  
Gabriele Siciliano ◽  
Michelangelo Mancuso
Keyword(s):  
Alzheimer’S Disease ◽  
Amyotrophic Lateral Sclerosis ◽  
Neurodegenerative Diseases ◽  
Mitochondrial Dysfunction ◽  
Huntington's Disease ◽  
Neurodegenerative Disorders ◽  
Molecular Abnormalities ◽  
Lateral Sclerosis ◽  
Lines Of Evidence

Many lines of evidence suggest that mitochondria have a central role in ageing-related neurodegenerative diseases. However, despite the evidence of morphological, biochemical and molecular abnormalities in mitochondria in various tissues of patients with neurodegenerative disorders, the question “is mitochondrial dysfunction a necessary step in neurodegeneration?” is still unanswered. In this review, we highlight some of the major neurodegenerative disorders (Alzheimer's disease, Parkinson's disease, Amyotrophic lateral sclerosis and Huntington's disease) and discuss the role of the mitochondria in the pathogenetic cascade leading to neurodegeneration.

scholarly journals Peroxisome Proliferator-Activated Receptor-γin Amyotrophic Lateral Sclerosis and Huntington’s Disease

PPAR Research ◽  
2008 ◽  
Vol 2008 ◽  
pp. 1-8 ◽  
Author(s):  
Mahmoud Kiaei
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Mouse Model ◽  
Neurodegenerative Diseases ◽  
Huntington's Disease ◽  
Transgenic Mouse ◽  
Transgenic Mouse Model ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
G93a Sod1 ◽  
Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a debilitating and one of the most common adult-onset neurodegenerative diseases with the prevalence of about 5 per 100 000 individuals. It results in the progressive loss of upper and lower motor neurons and leads to gradual muscle weakening ultimately causing paralysis and death. ALS has an obscure cause and currently no effective treatment exists. In this review, a potentially important pathway is described that can be activated by peroxisome proliferator-activated receptor-γ(PPAR-γ) agonists and has the ability to block the neuropathological damage caused by inflammation in ALS and possibly in other neudegenerative diseases like Huntington's disease (HD). Neuroinflammation is a common pathological feature in neurodegenerative diseases. Therefore, PPAR-γagonists are thought to be neuroprotective in ALS and HD. We and others have tested the neuroprotective effect of pioglitazone (Actos), a PPAR-γagonist, in G93A SOD1 transgenic mouse model of ALS and found significant increase in survival of G93A SOD1 mice. These findings suggest that PPAR-γmay be an important regulator of neuroinflammation and possibly a new target for the development of therapeutic strategies for ALS. The involvement of PPAR-γin HD is currently under investigation, one study finds that the treatment with rosiglitazone had no protection in R6/2 transgenic mouse model of HD. PPAR-γcoactivator-1α(PGC-1α) is a transcriptional coactivator that works together with combination of other transcription factors like PPAR-γin the regulation of mitochondrial biogenesis. Therefore, PPAR-γis a possible target for ALS and HD as it functions as transcription factor that interacts with PGC-1α. In this review, the role of PPAR-γin ALS and HD is discussed based on the current literature and hypotheses.

scholarly journals Common Factors in Neurodegeneration: A Meta-Study revealing Shared Patterns on a Multi-Omics Scale

2020 ◽  
Author(s):  
Nicolas Ruffini ◽  
Susanne Klingenberg ◽  
Susann Schweiger ◽  
Susanne Gerber
Keyword(s):  
Alzheimer’S Disease ◽  
Parkinson’S Disease ◽  
Alzheimer's Disease ◽  
Parkinson's Disease ◽  
Amyotrophic Lateral Sclerosis ◽  
Neurodegenerative Diseases ◽  
Huntington's Disease ◽  
Proteomic Data ◽  
Go Terms ◽  
Lateral Sclerosis

Neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and Amyotrophic Lateral Sclerosis are heterogeneous, progressive diseases with frequently overlapping symptoms characterized by a loss of neurons. Studies suggested relations between neurodegenerative diseases for many years, e.g., regarding the aggregation of toxic proteins or triggering endogenous cell death pathways. Within this study, publicly available genomic, transcriptomic and proteomic data were gathered from 188 studies and more than one million patients to detect shared genetic patterns between the neurodegenerative diseases and the analyzed omics-layers within conditions. The results show a remarkably high number of shared genes between the transcriptomic and proteomic levels for all diseases while showing a significant relation between genomic and proteomic data only in some cases. A set of 139 genes was found to be differentially expressed in several transcriptomic experiments of all four diseases. These 139 genes showed overrepresented GO-Terms and pathways mainly involved in stress response, cell development, cell adhesion, and the cytoskeleton. Furthermore, the overlap of two and three omics-layers per disease were used to search for overrepresented pathways and GO-Terms. Taken together, we could confirm the existence of many relations between Alzheimer's disease, Parkinson's disease, Huntington's disease, and Amyotrophic Lateral Sclerosis on the transcriptomic and proteomic level by analyzing the pathways and GO-Terms arising in these intersections. The significance of the connection between the transcriptomic and proteomic data for all four analyzed neurodegenerative diseases showed that exploring these omics-layers simultaneously holds new insights that do not emerge from analyzing these omics-layers separately. Our data therefore suggests addressing human patients with neurodegenerative diseases as complex biological systems by integrating multiple underlying data sources.

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