The EU Joint Programme - Neurodegenerative Disease Research (JPND) initiative launched a new joint transnational call for multinational research projects on personalised medicine for neurodegenerative diseases. The call is launched in partnership with the European Commission and has a budget of ca. EUR 30 M.. Neurodegenerative diseases are debilitating and still largely untreatable conditions. They are characterised by a large variability in their origins, mechanisms and clinical expression. When searching for a medical solution, e.g. a treatment or an optimised approach for care, this large variability constitutes a major hurdle if not controlled. Indeed a treatment addressing one disease pathway may not be useful for all patients experiencing the relevant symptoms. Thus, one of the greatest challenges for treating neurodegenerative diseases is the deciphering of this variability.. The following neurodegenerative diseases are included in the call:. ...

Neitzel, J.; Watts, M.; Diehl-Schmid, J.; Ortner, M.; Grimmer, T.; Yakushev, I.; Bublak, P.; Preul, C.; Finke, K.; Sorg, C. (2016): Distinct subcortical atrophy patterns across four different neurodegenerative syndromes. In: Journal of Neurochemistry, Vol. 138: p. 385 ...

The human APOE gene, which codes for apolipoprotein E (apoE), has three major polymorphic alleles: ε2, ε3, and ε4 that give rise to amino acid substitutions. APOE-ε4 is a strong risk factor of sporadic Alzheimers disease (AD) but the reason why is still unknown despite intense research for more than 20 years. The aim of the study was to investigate if the concentrations of total apoE and the specific apoE isoforms in cerebrospinal fluid (CSF) differ between various neurodegenerative diseases and control individuals, as well as among the APOE genotypes. Quantification of total apoE and specific apoE isoforms (E2, E3, and E4) in CSF was performed using high-resolution parallel reaction monitoring mass spectrometry. In total, 1820 individuals were involved in the study including clinically diagnosed AD patients (n = 228), cognitively unimpaired (CU) patients (n = 896), and patients with other neurodegenerative disorders (n = 696). Follow-up data was available for 100 individuals, assessed at two time

Aggregation of misfolded proteins and the associated loss of neurons are considered as a hallmark of numerous neurodegenerative diseases. Optineurin is present in protein inclusions observed in various neurodegenerative diseases including amyotrophic lateral sclerosis (ALS), Huntingtons disease, Alzheimers disease, Parkinsons disease, Creutzfeld-Jacob disease and Picks disease. Optineurin deletion mutations have also been described in ALS patients. However, the role of optineurin in mechanisms of protein aggregation remains unclear. In this report, we demonstrate that optineurin recognized various protein aggregates via its C-terminal coiled-coil domain in a ubiquitin-independent manner. We also show that optineurin depletion significantly increase protein aggregation in HeLa cells and morpholino-silencing of the optineurin ortholog in zebrafish causes the motor axonopathy phenotype similar to a zebrafish model of ALS. A more severe phenotype is observed when optineurin is depleted in ...

Abstract Platelets play an important role in a variety of disorders viz; cardiovascular, psychosomatic, psychiatric, thrombosis, HIV/AIDS in addition to various neurodegenerative diseases (NDD). Recent evidence indicates that platelet react to divers

BACKGROUND & OBJECTIVE: Alzheimers disease (AD) and Parkinsons disease (PD) affect an increasing number of the elderly population worldwide. The existing treatments mainly improve the core symptoms of AD and PD in a temporary manner and cause alarming side effects. Naturally occurring flavonoids are well-documented for neuroprotective and neurorestorative effects against various neurodegenerative diseases. Thus, we analyzed the pharmacokinetics of eight potent natural products flavonoids for the druggability and discussed the neuroprotective and neurorestorative effects and the underlying mechanisms. CONCLUSION: This review provides valuable clues for the development of novel therapeutics against neurodegenerative diseases ...

Neurodegenerative diseases are among the most common causes of disability worldwide. Although neurodegenerative diseases are heterogeneous in both their clinical features and the underlying physiology, they are all characterised by progressive loss of specific neuronal populations. Recent experiment …

This book sheds new light on neurodegenerative disorders as systemic diseases. Classically, neuronal cell death was a hallmark of such disorders. However, it has become evident that neural dysfunction is more important in the pathophysiology of neurodegenerative disorders. More recently, the prionoid-spreading hypothesis of disease-causing molecules has attracted a great deal of attention. Therapeutic strategies thus must be reconsidered in the light that neurodegenerative disorders are indeed systemic diseases. The first part of this book introduces the concept of neurodegeneration in biology and pathophysiology. The second part focuses on clinical evaluation and biomarkers from the perspective of this new concept, while the third summarizes the risk factors of neurodegeneration. The fourth part of this work indicates future directions of treatment, and the final part discusses health promotion for prevention and quality of life. This book will be of interest to both researchers and medical ...

Neurodegenerative diseases affect millions of people worldwide, and Alzheimers disease and Parkinsons disease are the most common types. The risk of being affected by a neurodegenerative disease increases dramatically with age and despite substantial research and development investments, effective therapeutics for the millions of patients with neurodegenerative diseases remain elusive. This creates a critical need to improve our understanding of what causes neurodegenerative diseases and develop new approaches for treatment and prevention.. USC is uniquely positioned as one of the top research institutions in the nation with comprehensive neurodegenerative disease research capabilities from bench to bedside and back. USC is comprised of leading scientists contributing to better understanding of the pathogenesis and treatment of neurological disorders such as Alzheimers disease and stroke, and leading experts in big data neuro-informatics, neuroimaging, structure-based drug discovery, systems ...

Neurodegenerative diseases affect millions of people worldwide, and Alzheimers disease and Parkinsons disease are the most common types. More than five million Americans are living with Alzheimers disease, and at least 500,000 Americans live with Parkinsons disease, although some estimates are much higher.. Neurodegenerative diseases occur when nerve cells in the brain or peripheral nervous system lose function over time and ultimately die. Although treatments may help relieve some of the physical or mental symptoms associated with neurodegenerative diseases, there is currently no cure or way to slow disease progression.. The risk of being affected by a neurodegenerative disease increases dramatically with age. Population-wide health improvements have increased lifespan, which along with a larger generation of aging Americans means more people may be affected by neurodegenerative diseases in coming decades. This creates a critical need to improve our understanding of what causes ...

Living cells continually generate reactive oxygen species (ROS) through the respiratory chain during energetic metabolism. ROS at low or moderate concentration can play important physiological roles. However, an excessive amount of ROS under oxidative stress would be extremely deleterious. The central nervous system (CNS) is particularly vulnerable to oxidative stress due to its high oxygen consumption, weakly antioxidative systems and the terminal-differentiation characteristic of neurons. Thus, oxidative stress elicits various neurodegenerative diseases. In addition, chemotherapy could result in severe side effects on the CNS and peripheral nervous system (PNS) of cancer patients, and a growing body of evidence demonstrates the involvement of ROS in drug-induced neurotoxicities as well. Therefore, development of antioxidants as neuroprotective drugs is a potentially beneficial strategy for clinical therapy. In this review, we summarize the source, balance maintenance and physiologic functions of ROS,

Functional and structural connectivity measures, as assessed by means of functional and diffusion MRI, are emerging as potential intermediate biomarkers for Alzheimer disease (AD) and other disorders. This Review aims to summarize current evidence that connectivity biomarkers are associated with upstream and downstream disease processes (molecular pathology and clinical symptoms, respectively) in the major neurodegenerative diseases. The vast majority of studies have addressed functional and structural connectivity correlates of clinical phenotypes, confirming the predictable correlation with topography and disease severity in AD and frontotemporal dementia. In neurodegenerative diseases with motor symptoms, structural--but, to date, not functional--connectivity has been consistently found to be associated with clinical phenotype and disease severity. In the latest studies, the focus has moved towards the investigation of connectivity correlates of molecular pathology. Studies in cognitively healthy

ApoE is the main lipid-carrier protein in the brain and has a role in the transport and metabolism of many lipid classes. This is important because the brain is a fatty, lipid-rich organ. ApoE can take three different forms, and the consequences of these differences can profoundly affect processes like lipid homeostasis and neurodegeneration. One specific form, ApoE4, increases ones risk of developing Alzheimers by as much as eightfold. A recent thematic review series in the Journal of Lipid Research includes eight articles that explore the connections between brain lipids, ApoE and Alzheimers disease.. Lipid abnormalities are closely associated with various neurodegenerative diseases, said Ta-Yuan T.Y. Chang of Geisel School of Medicine at Dartmouth College. He and wife Catherine Chang have been researching cholesterol metabolism and its relationship to neurodegenerative diseases for more than four decades. As the coordinators of the series, they selected experts in their fields to ...

In a large multi-site study, the researchers identified more than 1,500 potential biomarkers in cerebrospinal fluid from patients with one of three neurodegenerative diseases: Alzheimers, Parksinsons, or dementia with Lewy bodies (DLB). Researchers identified different sets of potential biomarkers corresponding to each disease; each of the proteins are linked specifically to one of the diseases. The results appear in the new issue of the Journal of Alzheimers Disease.. Were getting very close to being able to use these biomarkers for the clinical diagnosis of Alzheimers and Parkinsons disease, and dementia with Lewy bodies, said the studys lead author, Dr. Jing Zhang, associate professor of pathology at the UW. His lab is at Harborview Medical Center. This is a major improvement on other biomarker detection techniques.. Alzheimers, Parkinsons, and other neurodegenerative diseases affect millions of people in the United States, and the toll of the diseases is expected to worsen as ...

Defects in kinesin-3 transport have been implicated in diverse genetic, developmental, neurodegenerative and cancer diseases. Despite their widespread functions and clinical importance, the mechanisms of kinesin-3 mediated intracellular transport, regulations and their deficiencies in the context of human diseases are largely unknown. The project will continue to investigating the members of this family at cellular, molecular, structural and single molecule level to gain fundamental insights into molecular mechanisms of neuronal transport systems and the implications for various neurodegenerative diseases caused by the defects in microtubule based transport system. We will use cultured hippocampal neurons and Caenorhabditis elegans as model systems ...

This programme of research is aimed at studying underlying mechanisms and treatments for the major neurodegenerative diseases - Alzheimers, Epilepsy, Parkinsons, and Huntingtons. Neurodegenerative diseases affect over 100,000 New Zealanders and this will markedly increase as the population ages.

The new research suggests that the cells may die because of naturally occurring gene variation in brain cells that were, until recently, assumed to be genetically identical. This variation - called somatic mosaicism - could explain why neurons in the temporal lobe are the first to die in Alzheimers, for example, and why dopaminergic neurons are the first to die in Parkinsons.. This has been a big open question in neuroscience, particularly in various neurodegenerative diseases, said neuroscientist Michael McConnell, PhD, of UVAs Center for Brain Immunology and Glia (BIG). What is this selective vulnerability? What underlies it? And so now, with our work, the hypotheses moving forward are that it could be that different regions of the brain actually have a different garden of these [variations] in young individuals and that sets up different regions for decline later in life.. A Most Unexpected Outcome. The finding emerged unexpectedly from McConnells investigations into schizophrenia. ...

This section examines evidence for neurovascular changes during normal ageing and for neurovascular and/or BBB dysfunction in various neurodegenerative diseases, as well as the possibility that vascular defects can precede neuronal changes.. Age-associated neurovascular changes. Normal ageing diminishes brain circulatory functions, including a detectable decay of CBF in the limbic and association cortices that has been suggested to underlie age-related cognitive changes77. Alterations in the cerebral microvasculature, but not changes in neural activity, have been shown to lead to age-dependent reductions in functional hyperaemia in the visual system in cats78 and in the sensorimotor cortex in pericyte-deficient mice33. Importantly, a recent longitudinal CBF study in neurologically normal individuals revealed that people bearing the apolipoprotein E (APOE) ɛ4allele - the major genetic risk factor for late-onset Alzheimers disease79, 80, 81 - showed greater regional CBF decline in brain regions ...

p,Striatal interneurons display a morphological and chemical heterogeneity that has been particularly well characterized in rats, monkeys and humans. By comparison much less is known of striatal interneurons in mice, although these animals are now widely used as transgenic models of various neurodegenerative diseases. The present immunohistochemical study aimed at characterizing striatal interneurons expressing calretinin (CR) in mice compared to those in squirrel monkeys and humans. The mouse striatum contains both small (9-12 μm) and medium-sized (15-20 μm) CR+ cells. The small cells are intensely stained with a single, slightly varicose and moderately arborized process. They occur throughout the striatum (77±9 cells/mm(3)), but prevail in the area of the subventricular zone and subcallosal streak, with statistically significant anteroposterior and dorsoventral decreasing gradients. The medium-sized cells are less intensely immunoreactive and possess 2-3 long, slightly varicose and poorly ...

Thanks in large part to the seminal work of Steve White and his colleagues, we appreciate the ordered complexity of the lipid bilayer and how it impacts the incorporation of integral membrane proteins as well as more peripherally associated proteins. Steves work also provides a vital foundation to tackle another challenge: cytotoxic oligomeric complexes which accumulate in various neurodegenerative diseases. These oligomers have a relatively fluid structure and interact with many different proteins in the cell, but their main target is thought to be the phospholipid membrane, either the plasma membrane or internal organelles such as the mitochondria. This fascinating encounter between two essentially fluid phases generates a more disordered membrane, and presumably promotes uncontrolled transport of small metal ions across the membrane barrier. Happily, this unwanted interaction may be suppressed by mobilizing the phospholipid bilayer into its own defense. Extruded nanolipoparticles (NLPs) ...

Title: Cannabinoids and Neurodegenerative Diseases. VOLUME: 8 ISSUE: 6. Author(s):Julian Romero and Jose Martinez-Orgado. Affiliation:Laboratorio de Investigacion, Hospital Universitario Fundacion Alcorcon and Centro de Investigacion Biomedica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), C/o Budapest 1, 28922, Alcorcon, Spain.. Keywords:Alzheimers disease, ischemia, neuroprotection, glia. Abstract: Although significant advances have taken place in recent years on our understanding of the molecular mechanisms of different neurodegenerative diseases, its translation into effective therapeutic treatments has not been as successful as could be expected. There is still a dramatic lack of curative treatments for the most frequent disorders and only symptomatic relief for many others. Under this perspective, the search for novel therapeutic approaches is demanding and significant attention and efforts have been directed to studying additional neurotransmission systems including the ...

Lou Gehrigs disease, known as amyotrophic lateral sclerosis or ALS, strikes healthy, middle-aged people seemingly at random. Of the major neurodegenerative diseases, it has the least hope for treatment and survival. Although mental capabilities stay intact, ALS paralyzes people,....... ...

Neurological disorders have a strong negative impact on the quality of life of affected patients, their close relatives as well as on the health economic system. Early diagnosis associated with better treatment outcomes remain difficult to reach. Similarly, misdiagnosis is frequent and can lead to the delivery of the wrong treatment to the patient. As a matter of fact, the therapeutic strategies developed to treat Alzheimers Disease (AD) and Parkinsons Disease (PD), two major neurodegenerative diseases, are unfortunately only effective for reducing the symptoms. This illustrates the lack of complete understanding of the mechanisms underlining neurodegeneration. In this context, this thesis aims to contribute to a precise comprehension of the synaptic transmission, at the cellular level, by providing a biocompatible brain interface capable of collecting neurochemicals while establishing a tight electrical connection with the cerebral tissues. The first part of this thesis deals with the design ...

Lou Gehrigs disease, known as amyotrophic lateral sclerosis or ALS, strikes healthy, middle-aged people seemingly at random. Of the major neurodegenerative diseases, it has the least hope for treatment and survival. Although mental capabilities stay intact, ALS paralyzes people,....... ...

DESCRIPTION (provided by applicant): Methylation is a ubiquitous covalent modification used to control the function of diverse biomolecules including hormones, neurotransmitters, xenobiotics, proteins, nucleic acids and lipids. More than 50 distinct methyltransferase (MTs) enzymes are present in humans, and they are being targeted for a broad range of diseases, but their involvement in neurodegenerative disease pathways is of special relevance. Modulation of neurotransmitter methylation is an emerging therapeutic strategy for the treatment of several neurodegenerative diseases, most notably Parkinsons and Alzheimers diseases, and DNA and protein MTs are also being targeted for neurodegenerative diseases and cancers of the CNS. Moreover, the involvement of some MT family members in disease pathways is intertwined with their role in metabolizing commonly prescribed drugs. The development of highly selective MT modulators is clearly a compelling medical priority. However, efforts to achieve this ...

An expert panel convened by the NIH found little evidence that Alzheimers, Parkinsons, and similar neurodegenerative diseases can be transmitted in a prion-like fashion, such as after contact with biological specimens or contaminated surgical instruments. Still, writing in the October Journal of Neuropathology and Experimental Neurology, the panel, led by Matthew Frosch, Massachusetts General Hospital, Boston, consider current research on this topic inadequate and recommend that critical questions be studied so any risk of iatrogenic spread can be truly assessed. The panel broadly agrees with a whitepaper a European working group recently published on the topic (Sep 2020 news). Toxic forms of amyloid-β, tau, and α-synuclein can act as seeds to coax misfolding and aggregation of normal versions of these proteins in healthy brains. For example, injecting minuscule amounts of toxic Aβ into mouse brain prompts rampant formation of amyloid plaques months later (Oct 2011 news). Researchers have ...

Neurodegenerative diseases are characterized by the loss of nerve cells. It is generally accepted that once the cells of the brain and spinal cord are damaged they are not easily regenerated. The three most common neurodegenerative diseases are Alzheimers disease, Parkinsons disease and Multiple Sclerosis.

A new firm, Yumanity therapeutics, has been launched with the goal of working on neurodegenerative diseases. Presently almost 50 million people worldwide suffer from multiple types of neurodegenerative disease. News on NewsHub.org

Abstract Neurodegenerative diseases are a heterogeneous, mostly age-associated group of disorders characterized by progressive neuronal loss, the most prevalent being Alzheimer disease. It is anticipated that, with continuously increasing life expectancy, these diseases will pose a serious social and health problem in the near feature. Meanwhile, however, their etiology remains largely obscure even though all possible novel clues are being thoroughly examined. In this regard, a concept has been proposed that p53, as a transcription factor controlling many vital cellular pathways including apoptosis, may contribute to neuronal death common to all neurodegenerative disorders. In this work, we review the research devoted to the possible role of p53 in the pathogenesis of these diseases. We not only describe aberrant changes in p53 level/activity observed in CNS regions affected by particular diseases but, most importantly, put special attention to the complicated reciprocal regulatory ties existing ...

TY - JOUR. T1 - Cytokine/neurotrophin interaction in the aged central nervous system. AU - Macdonald, Nancy J.. AU - Decorti, Francesco. AU - Pappas, Todd C.. AU - Taglialatela, Giulio. PY - 2000. Y1 - 2000. N2 - Age-associated neurodegenerative diseases such as Alzheimers disease are characterised by neuronal impairment that leads to cognitive deficits. As certain affected neurons depend on trophic factors such as neurotrophins (NTs), impairment in NT function has been suggested to be a component of neuronal damage associated with such disorders. Age-related neurodegenerative diseases are also characterised by high levels of proinflammatory cytokines such as tumour necrosis factor alpha (TNFα) in the CNS. Because TNFα receptors and certain NT receptors share a high degree of homology and are capable of activating similar signalling pathways, one possibility is that altered cytokine levels may affect NT function in the aged or diseased CNS. Here we wish briefly to review the evidence ...

SingHealth Foundation Grant. Overview. Our laboratorys interests lie in identification and verification of novel key molecular targets, signaling pathways or neuro-protective agents relevant to pathogenesis and therapy of debilitating human neurodegenerative diseases, including Alzheimers disease (AD), Parkinson disease (PD) and multiple sclerosis. To achieve it, cutting-edged high throughput screening works are being performed in the lab. First, the in vitro high throughput proteomics screening plus immuno-precipitation protocols as well as cellular and molecular techniques are utilized to search and identify new key molecular targets or novel signaling pathways relevant to pathogenesis and therapy in human neurodegenerative diseases. Second, in vitro high throughput chemical library screening is being performed to identify new neuro-protective agents to modulate identified new molecular targets or signaling pathways for future clinical drugs developments. Findings from in vitro ...

Neuronal cell loss contributes to the pathology of acute and chronic neurodegenerative diseases, including Alzheimers disease (AD). It remains crucial to identify molecular mechanisms sensitizing neurons to various insults and cell death. To date, the multifunctional, autophagy-related protein Beclin 1 has been shown to be both necessary and sufficient for neuronal integrity in neurodegenerative models associated with protein aggregation. Interestingly, besides its role in cellular homeostasis, Beclin 1 has also been ascribed a role in apoptosis. This makes it critical to elucidate whether Beclin 1 regulates neuronal death and survival across neurodegenerative conditions independent of protein clearance. Here, we provide experimental evidence for a direct functional link between proteolytic cleavage of Beclin 1 and apoptotic neuronal cell loss in two independent models of neurodegeneration in vivo. Proteolytic cleavage of Beclin 1 was characterized in lysates of human AD brain samples. We developed

Neurodegenerative diseases, such as Alzheimers disease (AD), Parkinsons disease (PD), amyotrophic lateral sclerosis (ALS) and Huntingtons disease (HD) are caused by the progressive loss of neuronal integrity or acute neuron injury such as stroke or trauma in the brain and spinal cord.1-3 Current therapeutic strategies for neurodegenerative diseases are mainly aimed to decrease CNS neuron damage or brain dysfunction by conferring neuroprotection and neurogenesis.4,5 Consequently, the development of effective therapeutic medicine or discovery of new biological targets with neurogenesis activities remains an urgent need in the treatment of neurodegenerative diseases. During the past decades, various kinds of receptors, ion channels and signaling pathways associated with neurogenesis activities have been identified as potential therapeutic targets for neurodegenerative diseases. Among these, the σ1 receptor has attracted wide attention.6 σ1 receptor is one of the subtype belonging to the σ ...

Many of the key findings in neurodegenerative disease are from MIND. SOD1, the most common mutation associated with ALS was identified at MIND. MIND researchers had a critical role in identifying every one of the Alzheimers genes that has been found except for ApoE. Additionally, the gene for Huntingtons disease, which has paved the way for greater understanding of the disease, was discovered at Mass General.. ...

Many neurodegenerative diseases are characterized by the conformational change of self-proteins into amyloidogenic, pathological conformers, which share structu...

Our research focuses on identifying pathophysiological consequences of widespread RNA dysregulation in neurodegeneration in order to design, develop and test novel strategies of neuroprotective therapies.. Widespread dysregulation of the RNA metabolism has been recognised as a key pathophysiological component causing at least four neurodegenerative disorders: motor neurone disease (MND), also called Amyotrophic Lateral Sclerosis (ALS), spinal muscular atrophy (SMA), Huntingtons disease (HD) and spinocerebellar ataxias (SCAs). Widespread alteration of the transcriptome has also been reported in normal ageing of the brain and many neurodegenerative disorders are late progressive adult-onset diseases. Neurodegeneration in Parkinsons disease (PD) or Alzheimers disease (AD) is also likely to exhibit and/or involve broad alteration of the RNA metabolism and of multiple biological processes.. Although some genetic causes of these often-fatal diseases are known, the multifactorial molecular ...

A team of researchers, led by scientists at the University of California, San Diego, have identified a key player in the dramatic loss of neurons in mice and fly models, a discovery that could help illuminate the role of mitochondrial dysfunction in human neurodegenerative disorders, such as Parkinsons disease.

As a model organism |i|Saccharomyces cerevisiae|/i| has greatly contributed to our understanding of many fundamental aspects of cellular biology in higher eukaryotes. More recently, engineered yeast models developed to study endogenous or heterologous proteins that lay at the root of a given disease have become powerful tools for unraveling the molecular basis of complex human diseases like neurodegeneration. Additionally, with the possibility of performing target-directed large-scale screenings, yeast models have emerged as promising first-line approaches in the discovery process of novel therapeutic opportunities against these pathologies. In this paper, several yeast models that have contributed to the uncovering of the etiology and pathogenesis of several neurodegenerative diseases are described, including the most common forms of neurodegeneration worldwide, Alzheimers, Parkinsons, and Huntingtons diseases. Moreover, the potential input of these cell systems in the development of more

During embryonic development, sensory and motor fibers interact to form nerves in the limbs. The research team led by Dr. Andrea Huber Brösamle of the Institute of Developmental Genetics of Helmholtz Zentrum München has now elucidated how this interaction functions at the molecular level: The cell surface receptor neuropilin-1 is present in both sensory and motor nerve fibers and controls their interaction in order to correctly regulate growth. We observed that motor and sensory axons were both able to guide and lead the formation of the spinal nerves of the arms and legs, said Rosa-Eva Hüttl and Heidi Söllner, lead authors of the study and doctoral students in Dr. Andrea Huber Brösamles research group. This finding surprised the authors because it had previously been assumed that the motor axons were always responsible for establishing the correct trajectories. In the same study, the researchers created a model to better elucidate structural changes in human neurodegenerative disorders ...

Peptides that act like small molecules are highly desirable as drug candidates for targeting larger proteins and peptide specific binding sites. Hybridtides are

Ayer AH, Wojta K, Ramos EM, Dokuru D, Chen JA, Karydas AM, Papatriantafyllou JD, Agiomyrgiannakis D, Kamtsadeli V, Tsinia N, Sali D, Gylys KH, Agosta F, Filippi M, Small GW, Bennett DA, Gearing M, Juncos JL, Kramer J, Lee SE, Yokoyama JS, Mendez MF, Chui H, Zarow C, Ringman JM, Kilic U, Babacan-Yildiz G, Levey A, DeCarli CS, Cotman CW, Boxer AL, Miller BL, Coppola G. Frequency of the TREM2 R47H Variant in Various Neurodegenerative Disorders.. Alzheimer disease and associated disorders, 2019 ...

Biometals in Neurodegenerative Diseases: Mechanisms and Therapeutics is an authoritative and timely resource bringing together the major findings in the field for ease of access to those working in the field or with an interest in metals and their role in brain function, disease, and as therapeutic targets. Chapters cover metals in Alzheimers Disease, Parkinsons Disease, Motor Neuron Disease, Autism and lysosomal storage disorders.. This book is written for academic researchers, clinicians and advanced graduate students studying or treating patients in neurodegeneration, neurochemistry, neurology and neurotoxicology. The scientific literature in this field is advancing rapidly, with approximately 300 publications per year adding to our knowledge of how biometals contribute to neurodegenerative diseases.. Despite this rapid increase in our understanding of biometals in brain disease, the fields of biomedicine and neuroscience have often overlooked this information. The need to bring the ...

Many questions remain about how and when CCSVI might play a role in nervous system damage and whether venous angioplasty is helpful in treating the symptoms of CCSVI. Utilizing intravascular ultrasound (IVUS,) this pilot study will provide data that will allow researchers to evaluate venous morphology pre- and post- percutaneous angioplasty and sub-classify valve morphology as related to treatment success by distinguishing vessels which are more responsive to treatment. In addition, this study will validate the safety of valvuloplasty in various neurodegenerative disorders that involve venous obstruction ...

Abnormal proteostasis due to alterations in protein turnover has been postulated to play a central role in several neurodegenerative diseases. Therefore, the development of techniques to quantify protein turnover in the brain is critical for understanding the pathogenic mechanisms of these diseases. We have developed a bolus stable isotope-labeling kinetics (SILK) technique coupled with multiple reaction monitoring mass spectrometry to measure the clearance of proteins in the mouse brain. Cohorts of mice were pulse labeled with 13 C6-leucine and the brains were isolated after pre-determined time points. The extent of label incorporation was measured over time using mass spectrometry to measure the ratio of labeled to unlabeled apolipoprotein E (apoE) and amyloid β (Aβ). The fractional clearance rate (FCR) was then calculated by analyzing the time course of disappearance for the labeled protein species. To validate the technique, apoE clearance was measured in mice that overexpress the low-density

This study is being conducted to better understand the role of inflammation in Parkinsons disease (PD) and Alzheimers disease (AD). The investigators plan to recruit 30 PD, 30 AD/Amnestic Mild Cognitive Impairment (aMCI), and 60 age matched healthy controls in this study to study the role of immune response in PD and AD.. The study involves up to two study visits involving brief questionnaires and blood draw of up to 250cc (approximately 17 tablespoons) to be collected. More ways to participate, including 1) smaller amount blood donation (up to 100cc per visit for 1-2 visits); and 2) participation via tele-visit and mobile phlebotomy visits (blood donation up to 50cc, ~5 tubes, by a certified mobile phlebotomist at home/location of choice) now available. ...

Neurodegenerative Diseases is a bimonthly, multidisciplinary journal for the publication and discussion of advances in research on all aspects of neurodegenerative diseases. The journal focuses on Alz

Parkinsons disease is a neurodegenerative disorder of unknown cause that particularly affects areas of the brain which are involved in movement control. Research studies confirm the value of motor learning in Parkinsons disease, as well as showing improvements as a result of training.. CuPiD will develop innovative rehabilitation based on new technology, the patients needs, the principles of motor learning in Parkinsons disease. CuPiD will contribute to the challenge of engaging patients with a chronic neurodegenerative disease in intensive exercise for a considerable length of time.. ...

Parkinsons disease is a neurodegenerative disorder of unknown cause that particularly affects areas of the brain which are involved in movement control. Research studies confirm the value of motor learning in Parkinsons disease, as well as showing improvements as a result of training.. CuPiD will develop innovative rehabilitation based on new technology, the patients needs, the principles of motor learning in Parkinsons disease. CuPiD will contribute to the challenge of engaging patients with a chronic neurodegenerative disease in intensive exercise for a considerable length of time.. ...

Proteins, the components of our body that execute, control and organize basically all functions in our cells, are made out of strings of amino acids, which - like an origami - are folded into specific and complex three-dimensional structures according to their desired functions. However, since folding and maintaining of such structures is highly sensitive to cellular or environmental stress, proteins can potentially misfold or form clumps (aggregates). Such undesired protein waste can be toxic for cells and may even lead to cell death. Because several human neurodegenerative diseases are known to be linked to an accumulation of abnormal protein aggregates, basic science aimed to understand how cells remove cellular garbage is elementary for designing strategies for a potential prevention or cure of such disorders. Scientists in the laboratory of Stefan Jentsch at the MPIB now successfully used bakers yeast for screening for new cellular waste disposal pathways. Kefeng Lu, a postdoctoral ...

TY - JOUR. T1 - Quantitative measurement of postural sway in mouse models of human neurodegenerative disease. AU - Hutchinson, D.. AU - Ho, V.. AU - Dodd, M.. AU - Dawson, H. N.. AU - Zumwalt, A. C.. AU - Schmitt, D.. AU - Colton, C. A.. PY - 2007/9/21. Y1 - 2007/9/21. N2 - Detection of motor dysfunction in genetic mouse models of neurodegenerative disease requires reproducible, standardized and sensitive behavioral assays. We have utilized a center of pressure (CoP) assay in mice to quantify postural sway produced by genetic mutations that affect motor control centers of the brain. As a positive control for postural instability, wild type mice were injected with harmaline, a tremorigenic agent, and the average areas of the 95% confidence ellipse, which measures 95% of the CoP trajectory values recorded in a single trial, were measured. Ellipse area significantly increased in mice treated with increasing doses of harmaline and returned to control values after recovery. We also examined postural ...

Series: Neuroscience Research Progress. BISAC: MED057000. Multiple advanced neuroimaging applications in various neurodegenerative diseases including Parkinsons disease (PD), frontotemporal dementia (FTD), vascular dementia (VaD) and autism spectrum disorder (ASD) are covered in this book. Relatively novel techniques such as integrated PET/MRI and independent component analysis (ICA)-based dual regression (DR) methods were developed to capture multi-level molecular/functional and structural/microstructural as well as high-order inter-network coordination abnormalities. For instance, both PET dopamine transporter and striatal binding ratio reductions in the caudate and putamen were found in PD, consistent with the diffusion tensor imaging (DTI) fractional anisotropy (FA) reduction and fMRI voxel-mirrored homotopic correlation (VMHC) in the substantia nigra (swallow tail sign signature of PD). Furthermore, dopamine storage and pathway labeled with the vesicular monoamine transporter tracer ...

Hexanucleotide repeat expansions of variable size in C9orf72 are the most prevalent genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia. Sense and antisense transcripts of the expansions are translated by repeat-associated non-AUG translation into five dipeptide repeat proteins (DPRs). Of these, the polyGR, polyPR and, to a lesser extent, polyGA DPRs are neurotoxic, with polyGA the most abundantly detected DPR in patient tissue. Trans-cellular transmission of protein aggregates has recently emerged as a major driver of toxicity in various neurodegenerative diseases. In vitro evidence suggests that the C9 DPRs can spread. However, whether this phenomenon occurs under more complex in vivo conditions remains unexplored. Here, we used the adult fly brain to investigate whether the C9 DPRs can spread in vivo upon expression in a subset of neurons. We found that only polyGA can progressively spread throughout the brain, which accumulates in the shape of aggregate-like puncta inside

Mutations in the Valosin containing protein (VCP) gene are the cause of various neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), a form of motor neuron disease, and a rare multisystem disease which affects muscle, bone and brain. VCP is involved in a lot of different functions in cells. We know that VCP is important…

Abnormal iron accumulation within the brain is associated with various neurodegenerative diseases; however, there is debate about whether milder disorders of systemic iron loading, such as haemochromatosis, affect the brain. Arguments on both sides of the debate are often based on some common assumptions that have not been rigorously tested by appropriate experimentation. Recent research from our lab has applied high-throughput molecular techniques such as microarray to models of dietary and genetic iron loading to identify subtle but important effects on molecular systems in the brain that may go undetected by other methods commonly used in the field. In this chapter, we review the existing research in animal models and human patients and discuss the strengths and limitations of the different approaches commonly used. Using our findings as an example, we argue that transcriptomic methods can provide unique insights into how systemic iron loading can affect the brain and suggest some basic ...

A link between DNA damage and the process of aging has been firmly established (1, 2). The brain in particular is a vulnerable organ that is plagued by various neurodegenerative disorders that have been related to aging, i.e. Alzheimer and Parkinson disease. The study of the early onset of age-related neurodegenerative diseases is challenging, because there are not many confident early molecular determinants that predict their development. Therefore, progeroid syndromes (showing premature aging) are often used as a model for segmental aging as they show consistent and predictive elements of the aging phenotype (e.g. cessation of growth and development, hearing loss, and severe and progressive neuron dysfunction) (1, 3). These accelerated aging syndromes have in common that they carry defects in one or multiple proteins involved in DNA damage repair mechanisms.. A well established progeroid mouse model is the excision repair cross-complementing group 1 (Ercc1)1 gene knock-out (4, 5). The ...

28 04 2020GABA or gamma-aminobutyric acid is the major inhibitory neurotransmitter in mammals brains GABA receptors are the most common single receptor found in the synapses where neurons communicate with each other There are two known types of GABA receptor: GABA-A which comprise the primary sites of sedative drug action and GABA-B which play a role in muscle tone regulation Abstract Current treatments for insomnia such as zolpidem (Ambien) and eszopiclone (Lunesta) are γ-aminobutyric acid type A (GABA A)-positive allosteric modulators that carry a number of side effects including the potential to disrupt cognition In an effort to develop better tolerated medicines we have identified dual orexin 1 and 2 receptor antagonists (DORAs) which promote sleep in Because the GABA receptor is abundant in the cortex and is very sensitive to damage it represents a reliable marker of neuronal integrity-for example in ischemic brain damage and in various neurodegenerative diseases Part of the GABA A ...

When Dr. Jeff Bradstreet unexpectedly and tragically died in the spring of 2015, many of us wondered what would happen to the research he was doing with GcMAF, Goleic, and Bravo yogurt, which he was using to help children with autism. To my great pleasure, I am pleased to report that the research has continued and treatment options have been expanded. We are now seeing even more powerful results for the treatment of autism, cancer, chronic Lyme, chronic fatigue syndrome, and various neurodegenerative diseases. Dr. Bradstreets previous research focused on the macrophage activating factors known as GcMAF and Goleic, which he used in his clinic. Dr. Bradstreet was able to help 3 out of 4 autistic children by treating them with GcMAF or Goleic. Approximately 20% to 25% of these children lost their autism diagnosis and another 50% experienced a reduction in autistic symptoms. After the European manufacturing facility for GcMAF and Goleic was raided and closed down in the first months of 2015, Dr. ...

Elevated expression of specific transposable elements (TEs) has been observed in several neurodegenerative disorders. TEs also can be active during normal neurogenesis. By mining a series of deep sequencing datasets of protein-RNA interactions and of gene expression profiles, we uncovered extensive binding of TE transcripts to TDP-43, an RNA-binding protein central to amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Second, we find that association between TDP-43 and many of its TE targets is reduced in FTLD patients. Third, we discovered that a large fraction of the TEs to which TDP-43 binds become de-repressed in mouse TDP-43 disease models. We propose the hypothesis that TE mis-regulation contributes to TDP-43 related neurodegenerative diseases.. ...

Researchers will present findings at the AANS Annual Scientific meeting of their studying testing if Intralaminar thalamic deep brain stimulation (ILN-DBS) could have an effect on dementia and other neurodegenerative diseases that cause severe cognitive dysfunction.

Recent studies in neurodegenerative conditions have increasingly highlighted that the same neuropathology can trigger different clinical phenotypes or, vice-versa, that similar phenotypes can be triggered by different neuropathologies. This evidence has called for the adoption of a pathology spectrum-based approach to study neurodegenerative proteinopathies. These conditions share brain deposition of abnormal protein aggregates, leading to aberrant biochemical, metabolic, functional, and structural changes. Positron emission tomography (PET) is a well-recognized and unique tool for the in vivo assessment of brain neuropathology, and novel PET techniques are emerging for the study of specific protein species. Today, key applications of PET range from early research and clinical diagnostic tools to their use in clinical trials for both participants screening and outcome evaluation. This position article critically reviews the role of distinct PET molecular tracers for different neurodegenerative ...

Current diagnostic approaches to neurodegenerative diseases are often flawed as they are often invasive and cannot effectively diagnose early-onset dementia. Antibody-based therapeutics for neurodegenerative diseases are very promising but often lack specificity to certain biomarkers and require invasive methods of administration such as a lumbar puncture. In this study I report a novel quantum-dot (QD) conjugated bispecific-antibody (BsAb) diagnosis system designed for Alzheimers disease. This structure is easy to synthesize and displays specificity to oligomeric amyloid-beta (Aβ), which is often present before Alzheimers symptoms starts to manifest. The bispecific antibody also binds with a weak affinity to transferrin receptors - thus potentially allowing it to cross the blood-brain barrier (BBB) via receptor-mediated transcytosis and reducing the necessity for extremely- invasive means of administration such as a lumbar puncture. The CdTe/ZnS QDs conjugated to the BsAb have multimodal, ...

The EU Joint Programme - Neurodegenerative Disease Research (JPND) has announced a EUR 30 million call for neurodegenerative disease research topped-up with EUR 10 million from the Horizon 2020 framework programme for research and innovation of the European Union.. Neurodegenerative diseases such as Alzheimers and Parkinsons are a truly global challenge. Most of these diseases remain incurable and are strongly linked with aging populations. Dementias alone affect more than 7 million people in Europe and their care is estimated to cost EUR 130 billion a year. The challenge facing the world of diagnosing, treating and caring for people affected by neurodegenerative diseases is extremely daunting and no single country alone has the expertise or resources necessary to tackle all of the big questions in this area.. JPND was established in 2009 to enable participating EU Member States to work together on the challenge of age-related neurodegenerative diseases, in particular Alzheimers. In the past ...

The role of lipids in autophagy and its implication in neurodegeneration - Neurodegenerative diseases are, at present, major socio-economic burdens without effective treatments and their increasing prevalence means that these diseases will be a challenge for future generations. Neurodegenerative diseases may differ in etiology and pathology but are often caused by the accumulation of dysfunctional and aggregation-prone proteins. Autophagy, a conserved cellular mechanism, deals with cellular stress and waste product build-up and has been shown to reduce the accumulation of dysfunctional proteins in animal models of neurodegenerative diseases. Historically, progress in understanding the precise function of lipids has traditionally been far behind other biological molecules (like proteins) but emerging works demonstrate the importance of lipids in the autophagy pathway and how the disturbance of lipid metabolism is connected to neurodegeneration. Here we review how altered autophagy and the disturbance of

The role of inflammation in the progression of neurodegenerative disease remains unclear. We have shown that systemic bacterial insults accelerate disease progression in animals and in patients with Alzheimers disease. Disease exacerbation is associated with exaggerated CNS inflammatory responses to systemic inflammation mediated by microglia that become primed by the underlying neurodegeneration. The impact of systemic viral insults on existing neurodegenerative disease has not been investigated. Polyinosinic:polycytidylic acid (poly I:C) is a toll-like receptor-3 (TLR3) agonist and induces type I interferons, thus mimicking inflammatory responses to systemic viral infection. In the current study we hypothesized that systemic challenge with poly I:C, during chronic neurodegenerative disease, would amplify CNS inflammation and exacerbate disease. Using the ME7 model of prion disease and systemic challenge with poly I:C (12 mg/kg i.p.) we have shown an amplified expression of IFN-alpha and ...

A type of white blood cell that is important to the immune system may provide hope for new therapies for amyotrophic lateral sclerosis (ALS), as well as other neurodegenerative diseases, according to a study published online today in the Proceedings of the National Academy of Sciences.

According to a new study, tetrahydrocannabinolic acid (THCA), a compound found in cannabis, may be useful in treating neurodegenerative and neuroinflammatory diseases.

GENETICS AND ENVIRONMENT. Each of the major neurodegenerative disorders may be familial in nature. HD is exclusively familial; it is transmitted by autosomal dominant inheritance, and the molecular mechanism of the genetic defect has been defined. Nevertheless, environmental factors importantly influence the age of onset and rate of progression of HD symptoms. PD, AD, and ALS are mostly sporadic without clear pattern of inheritance. But for each there are well-recognized genetic forms. For example, there are both dominant (α-synuclein, LRRK2) and recessive (parkin, DJ-1, PINK1) gene mutations that may give rise to PD. In AD, mutations in the genes coding for the amyloid precursor protein (APP) and proteins known as the presenilins (involved in APP processing) lead to inherited forms of the disease. Mutations in the gene coding for copper-zinc superoxide dismutase (SOD1) account for about 2% of the cases of adult-onset ALS. There are also genetic risk factors that influence the probability of ...

A drug that boosts activity in the brains garbage disposal system can decrease levels of toxic proteins associated with Alzheimers disease and other neurodegenerative disorders and improve cognition in mice, a new study by neuroscientists at Columbia University Medical Center has found.

Herbicides have been recognized as the main environmental factor associated with human neurodegenerative disorders such as Parkinsons disease(PD). Previous studies indicated that the exposure to glyphosate, a widely used herbicide, is possibly linked to Parkinsonism, however the underlying mechanis …

If you have a question about this talk, please contact Gabriella Heller.. Toxicity of misfolded proteins and mitochondrial dysfunction are key factors that promote age-associated functional neuronal decline and neurodegenerative disease across species. Although these neurotoxic challenges have long been considered to be cell-intrinsic, evidence now supports that misfolded human disease proteins originating in one neuron can be transferred to neighboring cells, a phenomenon proposed to promote pathology spread. Likewise, mitochondria can be sent out of the cell that made them for transcellular degradation by neighbors. We discovered and are characterizing a dramatic, but previously unknown, capacity of C. elegans adult neurons to extrude large (~5µM) vesicles that can include aggregated proteins (including human neurodegenerative disease proteins) and damaged mitochondria. Strikingly, extruded exopher contents can be found in both neighboring and remote cells. We suggest that throwing out the ...

Abstract: OBJECTIVE: While the causes of neuronal death in Parkinsons disease (PD) and other neurodegenerative disorders are still unknown, several mechanisms are under discussion: programmed vs. passive cell death (apoptosis vs. necrosis), mainly based on conflicting results on the rare presence or absence of DNA fragmentation in substantia nigra neurons using the in situ DNA-labeling (TUNEL) method. DESIGN/METHODS: In 4 cases of Parkinsons disease (PD), 2 cases of Dementia with Lewy bodies (DLB) and 3 age-matched controls, the TUNEL/ISEL method was used to detect DNA fragmentation in substantia nigra locus coeruleus and cerebral cortex [method by Gold et al. (1994)]. In addition, immunohistochemistry was performed for an array of apoptosis-related proteins, i.e. the recently described apoptosis specific protein cJun/AP1 (ASP), the proto-oncogenes c-Jun, c-Jun AP1, Bcl2, Bax, Bcl-x, p53, CD 95 (Fas/Apo-1), activated caspase 3, several heat shock proteins (alpha-B crystallin, ubiquitin), and ...

Significant progress has been made over the past two decades on the pathogenesis of individual neurodegenerative diseases, including Alzheimers disease (AD), amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). However, different neurodegenerative syndromes have been mainly studied mechanistically in isolation. There has been a lack of concerted effort to ascertain whether and how these pathogenic processes may be linked to one another. In the most recent issue of journal Acta Neuropathologica, Dr. Mingkuan Sun, William Bell and Katherine LaClair, co-first authored a report about cryptic exon incorporation in Alzheimers disease cases exhibiting TDP-43 pathology. This is the first evidence on how loss of TDP-43 function from neurons, a common shared feature with ALS and FTD, could contribute to pathogenesis of AD.. It has been known for years that other factors besides Aβ and tau also contribute to neurodegeneration and cognitive failure in AD. The most convincing evidence is ...

Bile acids, a structurally related group of molecules derived from cholesterol, have a long history as therapeutic agents in medicine, from treatment for primarily ocular diseases in ancient Chinese medicine to modern day use as approved drugs for certain liver diseases. Despite evidence supporting a neuroprotective role in a diverse spectrum of age-related neurodegenerative disorders, including several small pilot clinical trials, little is known about their molecular mechanisms or their physiological roles in the nervous system. We review the data reported for their use as treatments for neurodegenerative diseases and their underlying molecular basis. While data from cellular and animal models and clinical trials support potential efficacy to treat a variety of neurodegenerative disorders, the relevant bile acids, their origin, and the precise molecular mechanism(s) by which they confer neuroprotection are not known delaying translation to the clinical setting.

Jika anda yang sedang mencari informasi [beasiswa] [info] 8 PhD scholarships sponsored by the German Research Center for Neurodegenerative Diseases (DZNE), maka Beasiswa akan menyampaikan tentang [beasiswa] [info] 8 PhD scholarships sponsored by the German Research Center for Neurodegenerative Diseases (DZNE) seperti dibawah ini ...

Many neurodegenerative diseases are characterized by the early loss of select groups of cells in the brain, followed only later by more widespread degeneration. Understanding the cause of the enhanced vulnerability displayed by select cell groups may point towards the root causes of these diseases and lead to novel therapeutic targets. Professor Myriam Heimans lab studies the selective vulnerability and pathophysiology seen in two neurodegenerative diseases of the basal ganglia, Huntingtons disease and Parkinsons disease.. The easily recognizable ravages of Huntingtons disease and Parkinsons disease on normal motor control reflect the loss of either dopamine-producing cells (Parkinsons disease) or dopamine-receiving cells (Huntingtons disease) in the brain. Until fairly recently, patients afflicted with these diseases would be diagnosed mainly by these abnormal motor behaviors. However, it was not known why a patient was afflicted; no usually suspected causes existed. The last twenty ...

Central nervous system (CNS)-related disorders, including brain cancer, lysosomal storage disorders, traumatic brain or spinal cord injury, chronic pain, or chronic neurodegenerative diseases, such as Alzheimers, Parkinsons disease or Amyotrophic Lateral Sclerosis, still represent a major burden for the society and demand innovative and more efficacious therapeutic approaches. Indeed, delivering therapeutics to the CNS is challenging since the blood-brain barrier (BBB) must be overcome to gain access to brain cells. Moreover, monitoring drug biodistribution or target engagement is rarely feasible if not impossible, due to the limited accessibility to tissue sampling, with the exception of the cerebrospinal fluid (CSF). However, CSF analysis is not always fully informative, especially for those conditions where the analyte is not a soluble compound released in biological fluids.Recent advances in nanomaterial science and nanoparticles (NPs) technology have provided a great breakthrough in pharmacology

Nagoya, Japan - Frontotemporal lobar degeneration (FTLD) is a type of dementia that appears earlier in life than Alzheimers disease (AD). Both FTLD and AD, along with several other neurodegenerative diseases, are marked by the appearance and clustering of the protein tau in nerve cells. However, there is much left to be explored about this…

We primarily use human neurons made from induced pluripotent stem cells as well as in vitro protein aggregation models to delineate the pathogenic mechanisms of age-related neurodegenerative diseases such as Alzheimers and Parkinsons disease. Our group is largely focused on utilizing neurons from rare lysosomal diseases to study how alterations in biomolecule degradation pathways influence the accumulation and conformation of disease-linked proteins such as alpha-synuclein, abeta, and tau. Mechanistic insights gained from studies of rare lysosomal diseases are used as a way to view and elucidate the pathological mechanisms of common neurodegenerative diseases. Another major effort of the lab is to determine how amyloid formation influences cellular self-renewal mechanisms in neurons, such as lysosomal clearance of damaged macromolecules, and the effect on the aging process ...

Alzheimers disease (AD), also known as just Alzheimers, is a chronic neurodegenerative disease that usually starts slowly and gets worse over time. It is the cause of 60% to 70% of cases of dementia. The most common early symptom is difficulty in remembering recent events (short-term memory loss).[1] As the disease advances, symptoms can include problems with language, disorientation (including easily getting lost), mood swings, loss of motivation, not managing self care, and behavioural issues. As a persons condition declines, they often withdraw from family and society. Gradually, bodily functions are lost, ultimately leading to death. Although the speed of progression can vary, the average life expectancy following diagnosis is three to nine years.. The cause of Alzheimers disease is poorly understood. About 70% of the risk is believed to be genetic with many genes usually involved. Other risk factors include a history of head injuries, depression, or hypertension. The disease process is ...

Parkinsons disease is a chronic neurodegenerative disease that is characterized by the loss of dopamine-producing neurons in the substantia nigra region of the brain. There is also a simultaneous loss of norepinephrine-producing neurons in a region called the locus coeruleus. Administration of methyl phenyl tetrahydropyridine (MPTP) to laboratory animals is a common model for Parkinsons disease; however, MPTP does not cause the motor deficits seen in humans with Parkinsons disease. NIEHS-supported investigators tested mice to determine whether the loss of norepinephrine neurons was necessary for the motor deficits seen in Parkinsons disease. They used transgenic mice that totally lack norepinephrine altogether. The researchers detected no motor deficits in control mice treated with MPTP - despite an 80 percent reduction in the number of dopamine-producing cells. On the other hand, the norepinephrine-lacking mice exhibited motor deficits in most tests, along with other movement disorders, ...

Clinical trials for Alzheimers and other neurodegenerative diseases are expensive and slow, in part because they cannot find enough participants. Of the 5 million people with Alzheimers in the United States alone, many never learn about trial opportunities, and for rare dementias the pool of potential volunteers is small to begin with. Online registries that allow people to be contacted about trial opportunities in their area have sprung up to speed recruitment. Some registries educate members about the disease; others establish active patient communities (May 2011 news; Nov 2013 news). Most sites ask for minimal information at sign-up, usually name, email address, birth year, and zip code. After registering, people may choose to complete more detailed health questionnaires in order to be matched to trials. Most registries include people with or without a diagnosis. In Alzheimers, researchers are beginning to test treatments in people at pre-dementia stages. These participants are hard to ...

TY - JOUR. T1 - Neurodegenerative diseases and exposure to the environmental metals Mn, Pb, and Hg. AU - Charlet, Laurent. AU - Chapron, Yves. AU - Faller, Peter. AU - Kirsch, Regina. AU - Stone, Alan T.. AU - Baveye, Philippe C.. PY - 2012/10. Y1 - 2012/10. N2 - Metal ions appear to play an important role in several neurodegenerative (ND) diseases. Evidence suggests that metal ions bind directly to causative amyloidogenic proteins and modulate their aggregation into amyloids, considered to be a key event in the etiology of ND diseases. Apart from this well-documented binding of essential metals to amyloidogenic proteins, other, non-essential metal ions have been considered to be environmental hazards for neuronal disorders, but tight causative relations have yet to be established. The present article provides a review of the potential role of manganese, lead, and mercury as environmental risk factors in ND diseases, and covers in detail environmental availability of these metals, their uptake ...

Finding biomarkers that reflect the amount of peripheral nerve damage (peripheral neuropathies) and that the biomarker will quickly drop in value in response to to effective treatment are desired goals. The tools we need for developing biomarkers for equine neurodegenerative diseases are not available. These tools include a laboratory model for each neurodegenerative disease, putative treatments, and a money bin.. There is an alternate path leading to biomarker development and that is the horizon we are chasing. The biomarker quest project identifies natural cases of disease with neurodegeneration followed by evaluating the data from those cases. Sifting through the data is a process of eliminating the negative, selecting the positive, and interpreting the in-between. I hear a jingle in there somewhere! Generally diseases follow a typical course, or pathogenesis. Interpreting enough cases points toward the direction we should take and where to concentrate our assets. Often clues to a direction ...

The results described here support the conclusion that AT-1 is the ER membrane acetyl-CoA transporter and that its function is essential for the normal physiology of the cell. The recent identification of a missense mutation in AT-1 associated with SPG42 and the fact that AT-1 is upregulated in chronic neurodegenerative diseases such as sporadic ALS and late-onset (sporadic) AD point to a crucial role in disorders that are characterized by neuronal dysfunction and/or loss.. Although initially associated with nuclear and cytosolic proteins, covalent acetylation of the ε-amino group of lysine residues also occurs in the mitochondria (Schwer et al., 2006) and in the early secretory pathway (Costantini et al., 2007). In the secretory pathway, it appears to function as a new form of post-translational regulation of membrane proteins. We initially identified the acetylation machinery while analyzing the metabolism of BACE1 (Costantini et al., 2007). Following that initial finding, we have also shown ...

An increasing number of neurodegenerative diseases are being found to be associated with the abnormal accumulation of aggregated proteins in the brain. In Parkinsons disease, this process involves the aggregation of alpha-synuclein (α-syn) into intraneuronal inclusions. Thus, compounds that inhibit α-syn aggregation represent a promising therapeutic strategy as disease-modifying agents for neurodegeneration. The formation of α-syn amyloid aggregates can be reproduced in vitro by incubation of the recombinant protein. However, the in vitro aggregation of α-syn is exceedingly slow and highly irreproducible, therefore precluding fast high throughput anti-aggregation drug screening. Here, we present a simple and easy-to-implement in-plate method for screening large chemical libraries in the search for α-syn aggregation modulators. It allows us to monitor aggregation kinetics with high reproducibility, while being faster and requiring lower protein amounts than conventional aggregation assays. We

Pro-apoptotic signaling caused by down-modulation of KIAA0358 or expression of IG20-SV4 effectively induces spontaneous apoptosis and sensitization to TNFa-induced apoptosis in neuroblastoma cells. Methods and composition to enhance cell death in neuroblastoma are provided. Methods and compositions to reduce cell death in neurodegenerative disorders are provided.

Caution: Medical devices made by Scion NeuroStim have not received marketing authorization from the US Food & Drug Administration (FDA) for use in chronic neurodegenerative diseases such as Parkinsons Disease and are not available for sale. Neuromodulation medical devices made by Scion NeuroStim are covered by the following US patents, with other US and international patents pending ...

Environmental Factors in Neurodevelopmental and Neurodegenerative Disorders presents a state-of-the-art review of the effects of environmental contaminants on the development and degeneration of the human nervous system, brought together by world-leading experts in the field. Part One describes the adverse effects that the environment can have on neurological development, and how these effects may exhibit. Specific contaminants and their possible consequences of exposure are addressed (lead, methylmercury, alcohol), as well as specific disorders and the environmental factors associated with them, such as the effect of diet on attention deficit and hyperactivity disorders. Part Two tackles neurodegenerative disorders, specifically addressing their potential neurotoxic origins, and discussing the increasing interest in the effects that early exposure may have in later life. Environmental Factors in Neurodevelopmental and Neurodegenerative Disorders is an invaluable reference for those professionals

Destruction and death of neurons can lead to neurodegenerative diseases. One possible way to treat neurodegenerative diseases and damage of the nervous system is replacing damaged and dead neurons by cell transplantation. If new neurons can replace the lost neurons, patients may be able to regain the lost functions of memory, motor, and so on. Therefore, acquiring neurons conveniently and efficiently is vital to treat neurological diseases. In recent years, studies on reprogramming human fibroblasts into neurons have emerged one after another, and this paper summarizes all these studies. Scientists find small molecules and transcription factors playing a crucial role in reprogramming and inducing neuron production. At the same time, both the physiological microenvironment in vivo and the physical and chemical factors in vitro play an essential role in the induction of neurons. Therefore, this paper summarized and analyzed these relevant factors. In addition, due to the unique advantages of physical

The neurotransmitter glutamate has been implicated in multiple neurodegenerative studies. Researchers agree that glutamate excitotoxicity undoubtedly has a role in the pathogenesis of Alzheimer disease, the most common neurodegenerative pathology affecting the elderly population. Research suggests glutamate excitotoxicity accelerates the progression of Alzheimer disease.[12] Glutamate is also implicated in the pathogenesis of Parkinson disease. Mutations in genes encoding the parkin and DJ1 proteins are present in Parkinsons disease, which are involved in the regulation of excitatory glutamate synapses. These proteins may also protect neurons against glutamate excitotoxicity.[13][14]. Gamma-aminobutyric acid (GABA), the major inhibitory neurotransmitter in the central nervous system, is targeted in the treatment of anxiety disorder, insomnia, epilepsy, and other conditions. In particular, these drugs alter GABAergic function by targeting the GABAA and GABAB receptors.[15]. Not only does ...

Neurodegenerative diseases such as Alzheimer�s disease (AD) and Parkinson�s disease (PD) are currently considered as protein misfolding diseases. Determina...

People who suffer from REM sleep behavior disorder are at increased risk of developing Parkinsons disease and dementia as they age, a new study reports. Researchers report RBD causes a lack of dopamine in the brain, and this can contribute to the development of neurodegenerative diseases.... Read More... ...

By Eric Sauter Scientists from the Florida campus of The Scripps Research Institute have uncovered a potentially important new therapeutic target that could prevent stress-related cell death, a characteristic of neurodegenerative diseases such as Parkinsons, as well as heart attack and stroke. In the study, published recently in the journal ACS Chemical Biology, the scientists showed they could disrupt a specific interaction of a critical enzyme that would prevent cell death without harming other important enzyme functions. The enzyme in question is c-jun-N-terminal kinase (JNK), pronounced junk, which has been implicated in many processes in the bodys response to stresses, such as oxidative stress, protein misfolding, and metabolic disorder. JNK also plays an important role in nerve cell survival and has become a target for drugs to treat neurodegenerative disorders such as Parkinsons disease. In recent studies, JNK has been found to migrate to the mitochondria-the part of the cell that ...

Notification may be sought. Participants may additionally consent to banking their DNA for use in future genetic research studies into neurodegenerative diseases. The blood drawn for use in the main study will also be used for extracting the DNA that will be stored for use in future research. Alternatively, specific studies on these samples may be abandoned, but data will be kept for 5 years after publication. The biospecimens and data have been provided for genetic research, for clinical, pathologic and genetic correlations, to try and identify the molecular basis of Parkinson Syndrome and related neurodegenerative disorders. The biospecimens may be destroyed or returned to collaborating Institutions, at their request and at any time. Similarly, individuals have the rights to withdraw their participation. The specific collaborating Institution only needs to notify Dr. Farrer (or the database administrator) to remove a record/sample.. ...