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Other Neurodegenerative Conditions (other + neurodegenerative_condition)
Selected AbstractsExamination of intravenous and intra-CSF protein delivery for treatment of neurological diseaseEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 6 2009Kim M. Hemsley Abstract Mucopolysaccharidosis type IIIA is a neurodegenerative lysosomal storage disorder characterized by progressive loss of learned skills, sleep disturbance and behavioural problems. Absent or greatly reduced activity of sulphamidase, a lysosomal protein, results in intracellular accumulation of heparan sulphate. Subsequent neuroinflammation and neurodegeneration typify this and many other lysosomal storage disorders. We propose that intra-cerebrospinal fluid protein delivery represents a potential therapeutic avenue for treatment of this and other neurodegenerative conditions; however, technical restraints restrict examination of its use prior to adulthood in mice. We have used a naturally-occurring Mucopolysaccharidosis type IIIA mouse model to determine the effectiveness of combining intravenous protein replacement (1 mg/kg) from birth to 6 weeks of age with intra-cerebrospinal fluid sulphamidase delivery (100 ,g, fortnightly from 6 weeks) on behaviour, the level of heparan sulphate-oligosaccharide storage and other neuropathology. Mice receiving combination treatment exhibited similar clinical improvement and reduction in heparan sulphate storage to those only receiving intra-cerebrospinal fluid enzyme. Reductions in micro- and astrogliosis and delayed development of ubiquitin-positive lesions were seen in both groups. A third group of intravenous-only treated mice did not exhibit clinical or neuropathological improvements. Intra-cerebrospinal fluid injection of sulphamidase effectively, but dose-dependently, treats neurological pathology in Mucopolysaccharidosis type IIIA, even when treatment begins in mice with established disease. [source] Impaired inhibitory G-protein function contributes to increased calcium currents in rats with diabetic neuropathyJOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 2 2002KE Hall There is a growing body of evidence that sensory neuropathy in diabetes is associated with abnormal calcium signaling in dorsal root ganglion (DRG) neurons. Enhanced influx of calcium via multiple high-threshold calcium currents is present in sensory neurons of several models of diabetes mellitus, including the spontaneously diabetic BioBred/Worchester (BB/W) rat and the chemical streptozotocin (STZ)-induced rat. We believe that abnormal calcium signaling in diabetes has pathologic significance as elevation of calcium influx and cytosolic calcium release has been implicated in other neurodegenerative conditions characterized by neuronal dysfunction and death. Using electrophysiologic and pharmacologic techniques, the present study provides evidence that significant impairment of G-protein-coupled modulation of calcium channel function may underlie the enhanced calcium entry in diabetes. N- and P-type voltage-activated, high-threshold calcium channels in DRGs are coupled to mu opiate receptors via inhibitory G(o)-type G proteins. The responsiveness of this receptor coupled model was tested in dorsal root ganglion (DRG) neurons from spontaneously-diabetic BB/W rats, and streptozotocin-induced (STZ) diabetic rats. Intracellular dialysis with GTPgammaS decreased calcium current amplitude in diabetic BB/W DRG neurons compared with those of age-matched, nondiabetic controls, suggesting that inhibitory G-protein activity was diminished in diabetes, resulting in larger calcium currents. Facilitation of calcium current density (I(DCa)) by large-amplitude depolarizing prepulses (proposed to transiently inactivate G proteins), was significantly less effective in neurons from BB/W and STZ-induced diabetic DRGs. Facilitation was enhanced by intracellular dialysis with GTPgammaS, decreased by pertussis toxin, and abolished by GDPbetaS within 5 min. Direct measurement of GTPase activity using opiate-mediated GTPgamma[(35)S] binding, confirmed that G-protein activity was significantly diminished in STZ-induced diabetic neurons compared with age-matched nondiabetic controls. Diabetes did not alter the level of expression of mu opiate receptors and G-protein alpha subunits. These studies indicate that impaired regulation of calcium channels by G proteins is an important mechanism contributing to enhanced calcium influx in diabetes. [source] What is the basis of transmissible spongiform encephalopathy induced neurodegeneration and can it be repaired?NEUROPATHOLOGY & APPLIED NEUROBIOLOGY, Issue 1 2002J. R. FraserArticle first published online: 8 APR 200 Once an animal becomes infected with a prion disease, or transmissible spongiform encephalopathy (TSE), the progression of infection is relentless and inevitably fatal, although often with such prolonged incubation periods that an alternative cause of death can intervene. Infection has been compared to ,setting a clock' which then runs inexorably as the disease spreads, usually through the lymphoreticular system and then via peripheral nerves to the central nervous system (CNS), although the mechanism controlling the protracted progression is not known. Clinical disease develops as characteristic degenerative changes in the CNS progress, but the molecular basis for this pathology is not clear, particularly the relationship between the deposition of abnormal PrP and neuronal dysfunction. Recent research has identified several means of slowing (if not stopping) the clock when infection has not yet reached the CNS; although the potential for later stage therapies seems limited, neuroprotective strategies which have been shown to be effective in other neurodegenerative conditions may also ameliorate TSE induced CNS pathology. This review focuses on our current knowledge of the key events following infection of the CNS and the opportunities for intervention once the CNS has become infected. [source] FUS-immunoreactive inclusions are a common feature in sporadic and non-SOD1 familial amyotrophic lateral sclerosisANNALS OF NEUROLOGY, Issue 6 2010Han-Xiang Deng MD Objective Amyotrophic lateral sclerosis (ALS) is a fatal disorder of motor neuron degeneration. Most cases of ALS are sporadic (SALS), but about 5 to 10% of ALS cases are familial (FALS). Recent studies have shown that mutations in FUS are causal in approximately 4 to 5% of FALS and some apparent SALS cases. The pathogenic mechanism of the mutant FUS-mediated ALS and potential roles of FUS in non-FUS ALS remain to be investigated. Methods Immunostaining was performed on postmortem spinal cords from 78 ALS cases, including SALS (n = 52), ALS with dementia (ALS/dementia, n = 10), and FALS (n = 16). In addition, postmortem brains or spinal cords from 22 cases with or without frontotemporal lobar degeneration were also studied. In total, 100 cases were studied. Results FUS-immunoreactive inclusions were observed in spinal anterior horn neurons in all SALS and FALS cases, except for those with SOD1 mutations. The FUS-containing inclusions were also immunoreactive with antibodies to TDP43, p62, and ubiquitin. A fraction of tested FUS antibodies recognized FUS inclusions, and specific antigen retrieval protocol appeared to be important for detection of the skein-like FUS inclusions. Interpretation Although mutations in FUS account for only a small fraction of FALS and SALS, our data suggest that FUS protein may be a common component of the cellular inclusions in non-SOD1 ALS and some other neurodegenerative conditions, implying a shared pathogenic pathway underlying SALS, non-SOD1 FALS, ALS/dementia, and related disorders. Our data also indicate that SOD1-linked ALS may have a pathogenic pathway distinct from SALS and other types of FALS. ANN NEUROL 2010;67:739,748 [source] 2452: Patients in the DARC: drops revealing retinal ganglion cells in vivoACTA OPHTHALMOLOGICA, Issue 2010MF CORDEIRO Purpose To provide a review of current & future DARC imaging technologies and their application to neuroprotection Methods Currently, lowering IOP remains the only clinical therapy available in the treatment of glaucoma, despite the evidence that vision loss can continue in the presence of "significant" IOP reduction. Neuroprotection has been increasingly recognized as an important alternative treatment approach, but its emergence has also highlighted the need for both better defined end-points in clinical glaucoma research, as well as earlier and better detection and measures of progression. This could have been a factor in the recent memantine trial. A recent FDA/NEI meeting on end-points in glaucoma emphasized the need for new measurements. As the RGC is the primary injured neuron in this disease, it would seem logical that any modality that could directly measure RGC dysfunction and disease would be ideal. Perhaps the greatest changes that we have encountered recently are in the field of imaging technologies, which have only relatively recently been applied to the eye. Results Advances in this area have allowed unprecedented in vivo access to the retinal layers, using many different properties of light to differentiate cellular structures. DARC is a technology shortly to enter clinical trials which allows the visualization of "sick" RGCs. Conclusion Over the next few years, developments in therapy & diagnostic using DARC should offer great potential in glaucoma and other neurodegenerative conditions. Commercial interest [source] When late life brings a diagnosis of Alzheimer's Disease and early life brought trauma.CLINICAL PSYCHOLOGY AND PSYCHOTHERAPY (AN INTERNATIONAL JOURNAL OF THEORY & PRACTICE), Issue 3 2003A cognitive-analytic understanding of loss of mind This paper contrasts the loss of mind from the loss of brain cells in Alzheimer's Disease and other neurodegenerative conditions with the threats to one's mind from the mindlessness of others from a cognitive-analytic perspective. Case studies are presented that show how the therapeutic framework of Cognitive-Analytic Therapy (CAT: Ryle 1990, 1995, 1997) can bring containment for both client and therapist for clients facing this dilemma, particularly when past trauma is potentially overwhelming. This is set in a dialogue with the pioneering work of Tom Kitwood (1990, 1995, 1997) in dementia care, in which Kitwood's thesis of the ,malignant social psychology' surrounding people with dementia is re-stated in terms of ,reciprocal roles' developed in Cognitive-Analytic Therapy. Copyright © 2003 John Wiley & Sons, Ltd. [source] | ||||||||||