Advanced magnetic resonance imaging of neurodegenerative diseases

Magnetic resonance imaging (MRI) is playing an increasingly important role in the study of neurodegenerative diseases, delineating the structural and functional alterations determined by these conditions. Advanced MRI techniques are of special interest for their potential to characterize the signature of each neurodegenerative condition and aid both the diagnostic process and the monitoring of disease progression. This aspect will become crucial when disease-modifying (personalized) therapies will be established. MRI techniques are very diverse and go from the visual inspection of MRI scans to more complex approaches, such as manual and automatic volume measurements, diffusion tensor MRI, and functional MRI. All these techniques allow us to investigate the different features of neurodegeneration. In this review, we summarize the most recent advances concerning the use of MRI in some of the most important neurodegenerative conditions, putting an emphasis on the advanced techniques.     

Self‐evolving oxidative stress with identifiable pre‐ and postmitochondrial phases in PC12 cells

During the neurodegenerative process in several brain diseases, oxidative stress is known to play important roles in disease severity and evolution. Although early events of stress, such as increased lipid peroxidation and decreased superoxide dismutase, are known to characterize early onsets of these diseases, little is known about the events that participate in maintaining the chronic evolving phase influencing the disease progression in neurons. Here, we used differentiated PC12 cells to identify premitochondrial and postmitochondrial events occurring during the oxidative stress cascade leading to apoptosis. Our data indicate that an acute and strong oxidative impulse (500 μM H₂O₂, 30 min) can induce, in this model, a 24‐hr self‐evolving stress, which advances from a premitochondrial phase characterized by lysosomes and cathepsin B and D translocations to cytosol and early mitochondrial membrane hyperpolarization. This phase lasts for about 5 hr and is followed by a postmitochondrial phase distinguished by mitochondrial membrane depolarization, reactive oxygen species increase, caspase‐9 and caspase‐3 activations, and apoptosis. Inhibition of cathepsins B and D suggests that cells can be protected at the premitochondrial phase of stress evolution and that new cathepsins regulators, such as glycosaminoglycans mimetics, can be considered as new therapeutic prototypes for neurodegeneration. Insofar as early oxidative stress markers have been related to the early onset of neurodegeneration, strategies protecting cells at the premitochondrial phase of oxidative stress may have important therapeutic applications. © 2012 Wiley Periodicals, Inc.     

Huntington's disease: Current and future therapeutic prospects

Huntington's disease is a progressive neurodegenerative disorder for which therapies are woefully inadequate and do not prevent inevitable progression. Currently approved therapies are primarily aimed at treating chorea, but do not address the more clinically meaningful motor, behavioral, and cognitive features of the disease. However, there are a number of promising new therapies that are currently being studied in the laboratory, and in the clinic. This article will review the wide variety of therapies currently being tested, the advances in clinical trials and end points, and the many potentially relevant new targets. © 2018 International Parkinson and Movement Disorder Society     

Proteomics of human neurodegenerative diseases

The technology, experimental approaches, and bioinformatics that support proteomic research are evolving rapidly. The application of these new capabilities to the study of neurodegenerative diseases is providing insight into the biochemical pathogenesis of neurodegeneration as well as fueling major efforts in biomarker discovery. Here, we review the fundamentals of commonly used proteomic approaches and the outcomes of these investigations with autopsy and cerebrospinal fluid samples from patients with neurodegenerative diseases.     

Structural and functional magnetic resonance imaging in psychiatric disorders.

OBJECTIVE: To report on recent advances in both structural and functional brain imaging studies in psychiatry and to highlight their importance for the field. METHOD: We reviewed recently published articles dealing with such advances and abstracted them into a selective review of the field. RESULTS: Some of the more important trends include integration of genetic information into research studies, use of novel quantitative image measurement techniques, studies of new subject populations, the use of pharmacologic probes in functional magnetic resonance imaging (fMRI) studies, the incorporation of elements of virtual reality into fMRI task stimuli, and the methodological innovation of hyperscanning. CONCLUSIONS: A whole series of new approaches and techniques are resulting in rapid advances in neuroimaging in psychiatry. Several of these show the potential for clinical translation.     

Gene transfer therapy for neurodegenerative disorders

Recent advances in gene transfer technology have led to promising new therapies for neurodegenerative disorders. This article will review methods of gene transfer therapy and applications of these techniques to both genetic and sporadic neurodegenerative illnesses. The article will focus on Parkinson's disease, Huntington's disease, and Alzheimer's disease. Several promising gene therapy approaches to these diseases are being pursued both in animal models and in early human trials. Initial safety–tolerability results from these trials appear promising. It is therefore likely that the number of human trials of gene therapy for neurodegenerative disorders will increase over the coming years. © 2007 Movement Disorder Society     

Suicide prevention in military organizations

Summary

Alzheimer's disease (AD) is a heterogeneous neurodegenerative disorder characterized pathologically by amyloid-beta plaques, neurofibrillary tangles and neuronal loss. Its fundamental cause(s) and the pathological cascades leading to clinical symptoms remain unknown. Lipids and lipid peroxidation products have important roles in the homeostasis of the central nervous system. As well, lipid transport genes and vascular changes associated with peripheral dyslipidemia have been associated with an increased risk of AD. The present review discusses ways in which lipids may be involved in the pathogenesis of AD-associated neurodegeneration through their roles as neuronal structural components, cell modulators, or second messengers. Given the many possibilities through which lipids may be directly involved in or contribute to the pathogenesis of AD, the use of lipids as biomarkers for disease progression is discussed, as are other avenues for future research.     

Lipids and the pathogenesis of Alzheimer's disease: is there a link?

Alzheimer's disease (AD) is a heterogeneous neurodegenerative disorder characterized pathologically by amyloid-beta plaques, neurofibrillary tangles and neuronal loss. Its fundamental cause(s) and the pathological cascades leading to clinical symptoms remain unknown. Lipids and lipid peroxidation products have important roles in the homeostasis of the central nervous system. As well, lipid transport genes and vascular changes associated with peripheral dyslipidemia have been associated with an increased risk of AD. The present review discusses ways in which lipids may be involved in the pathogenesis of AD-associated neurodegeneration through their roles as neuronal structural components, cell modulators, or second messengers. Given the many possibilities through which lipids may be directly involved in or contribute to the pathogenesis of AD, the use of lipids as biomarkers for disease progression is discussed, as are other avenues for future research.     

The Treatment of Sleep Dysfunction in Neurodegenerative Disorders

Sleep dysfunction is highly prevalent across the spectrum of neurodegenerative conditions and is a key determinant of quality of life for both patients and their families. Mounting recent evidence also suggests that such dysfunction exacerbates cognitive and affective clinical features of neurodegeneration, as well as disease progression through acceleration of pathogenic processes. Effective assessment and treatment of sleep dysfunction in neurodegeneration is therefore of paramount importance; yet robust therapeutic guidelines are lacking, owing in part to a historical paucity of effective treatments and trials. Here, we review the common sleep abnormalities evident in neurodegenerative disease states and evaluate the latest evidence for traditional and emerging interventions, both pharmacological and nonpharmacological. Interventions considered include conservative measures, targeted treatments of specific clinical sleep pathologies, established sedating and alerting agents, melatonin, and orexin antagonists, as well as bright light therapy, behavioral measures, and slow-wave sleep augmentation techniques. We conclude by providing a suggested framework for treatment based on contemporary evidence and highlight areas that may emerge as major therapeutic advances in the near future.Key Words: Sleep, Insomnia, Neurodegeneration, Dementia, Alzheimer’s, Parkinson’s     

Astrocytes: a double-edged sword in neurodegenerative diseases

Astrocytes play multifaceted and vital roles in maintaining neurophysiological function of the central nervous system by regulating homeostasis, increasing synaptic plasticity, and sustaining neuroprotective effects. Astrocytes become activated as a result of inflammatory responses during the progression of pathological changes associated with neurodegenerative disorders. Reactive astrocytes(neurotoxic A1 and neuroprotective A2) are triggered during disease progression and pathogenesis due to neuroinflammation and ischemia. However, only a limited body of literature describes morphological and functional changes of astrocytes during the progression of neurodegenerative diseases. The present review investigated the detrimental and beneficial roles of astrocytes in neurodegenerative diseases reported in recent studies, as these cells have promising therapeutic potential and offer new approaches for treatment of neurodegenerative diseases.     

Illuminating Neural Circuits in Alzheimer’s Disease

Alzheimer’s disease (AD) is the most common neurodegenerative disorder and there is currently no cure. Neural circuit dysfunction is the fundamental mechanism underlying the learning and memory deficits in patients with AD. Therefore, it is important to understand the structural features and mechanisms underlying the deregulated circuits during AD progression, by which new tools for intervention can be developed. Here, we briefly summarize the most recently established cutting-edge experimental approaches and key techniques that enable neural circuit tracing and manipulation of their activity. We also discuss the advantages and limitations of these approaches. Finally, we review the applications of these techniques in the discovery of circuit mechanisms underlying β-amyloid and tau pathologies during AD progression, and as well as the strategies for targeted AD treatments.     

Modeling of Alzheimer’s disease using viral vectors

In this review, we focused on modern methods of modeling of Alzheimer’s disease. The discovery of the relationship between the metabolism of several proteins and the progression of neurodegeneration has provided new opportunities for modeling of neurodegenerative diseases. Progress in gene engineering techniques has made it possible to develop models based on targeted neuronal expression of these proteins in the brain of laboratory animals. In these models, viral vectors are used as a tool for gene delivery and transfer. The specific features, advantages, and disadvantages of this approach are discussed in the present review.     

Pathogenic role of ganglioside metabolism in neurodegenerative diseases

Ganglioside metabolism is altered in several neurodegenerative diseases, and this may participate in several events related to the pathogenesis of these diseases. Most changes occur in specific areas of the brain and their distinct membrane microdomains or lipid rafts. Antiganglioside antibodies may be involved in dysfunction of the blood–brain barrier and disease progression in these diseases. In lipid rafts, interactions of glycosphingolipids, including ganglioside, with proteins may be responsible for the misfolding events that cause the fibril and/or aggregate processing of disease‐specific proteins, such as α‐synuclein, in Parkinson's disease, huntingtin protein in Huntington's disease, and copper‐zinc superoxide dismutase in amyotrophic lateral sclerosis. Targeting ganglioside metabolism may represent an underexploited opportunity to design novel therapeutic strategies for neurodegeneration in these diseases. © 2014 Wiley Periodicals, Inc.     

Dysregulation of lipids in Alzheimer's disease and their role as potential biomarkers

The brain is highly enriched in lipids, and an intensive study of these lipids may be informative, not only of normal brain function but also of changes with age and in disease. In recent years, the development of highly sensitive mass spectrometry platforms and other high-throughput technologies has enabled the discovery of complex changes in the entire lipidome. This lipidomics approach promises to be a particularly useful tool for identifying diagnostic biomarkers for early detection of age-related neurodegenerative disease, such as Alzheimer's disease (AD), which has till recently been limited to protein- and gene-centric approaches. This review highlights known lipid changes affecting the AD brain and presents an update on the progress of lipid biomarker research in AD. Important considerations for designing large-scale lipidomics experiments are discussed to help standardize findings across different laboratories, as well as challenges associated with moving toward clinical application.     

Mechanisms by which metals promote events connected to neurodegenerative diseases

Although the exact causative phenomenon responsible for the onset and progression of neurodegenerative disorders is at present unresolved, there are some clues as to the mechanisms underlying these chronic diseases. This review addresses mechanisms by which endogenous or environmental factors, through interaction with redox active metals, may initiate a common cascade of events terminating in neurodegeneration.     

Signal transduction and neurosurvival in experimental models of brain injury

Brain injury and neurodegenerative disease are linked by their primary pathological consequence-death of neurons. Current approaches for the treatment of neurodegeneration are limited. In this review, we discuss animal models of human brain injury and molecular biological data that have been obtained from their analysis. In particular, signal transduction pathways that are associated with neurosurvival following injury to the brain are presented and discussed.