parkinson s disease basic mechanisms of neurodegeneration

... leading scientists in the field of neurobiology of Alzheimer s disease Alzheimer s disease attracted researchers from diverse academic fields, including clinical, basic and social sciences It is essential ... Chaperones GRP78BiP Fig PS1 mutations downregulate the signaling pathway of the unfolded protein response This scheme shows mechanisms of ER stress response Activation of PERK results in phosphorylation ... understanding of this formidable disease and to share new findings among researchers in the field Clinical and basic research of Alzheimer s disease has been the main interest of the Department of...

Ngày tải lên: 14/02/2014, 17:20

... Dunn 's test for posthoc comparisons when appropriate SPSS 12.0.1 for Windows (ACITS; The University of Texas at Austin, Austin, TX, USA) statistical software was used P < 0.05 was considered statistically ... Cases versus controls Decreased PC values (defined as

Ngày tải lên: 12/08/2014, 23:21

... overexpress the c-secretase complex components These assays are used to test the effects of detergent concentration, solvents and metals on the c-secretase cleavage of APP substrates These studies show ... of c-secretase activity Lastly, zinc causes structural changes in a c-secretase substrate and acts as an inhibitor of csecretase cleavage of APP Results Design of a novel APP c-secretase substrate ... vitro c-secretase assay with COS7-SPC993FLAG solubilized membranes To complement our MC99-3FLAG based in vitro c-secretase assays, an in vitro assay using COS7SPC99-3FLAG CHAPSO extracts was developed...

Ngày tải lên: 16/03/2014, 23:20

... lymph nodes and thus a suppression of the immune response (Schwab & Cyster, 2007) Sphingosine-Kinases Phosphorylation of sphingosine by the sphingosine-kinases (SphK1 and SphK2) generates S1 P (Kohama ... number of sphingolipidoses were described so far, like Gaucher s disease as the most frequent one, Niemann Pick A or B (NPA, NPB), Sandhoff disease, Tay Sachs disease and many others In Gaucher s disease, ... ceramidases GSLs are degraded by a subset of various specific catabolic enzymes in the endosomal/lysosomal compartments Sphingosine is subsequently phosphorylated by the sphingosine-kinases or 2,...

Ngày tải lên: 25/11/2015, 15:23

... relevance of cross-breeding experiments is strengthened if expression and deletion of the gene (s) results in the opposite outcome, or if the results are substantiated by in vitro studies or analyses of ... models of Alzheimer s disease dent differences in the speed of Ab accumulation Moreover, transgene expression can differ across generations and give rise to unstable Ab phenotypes because of loss ... Authors Journal compilation ª 2010 FEBS 1391 Animal models of Alzheimer s disease O Philipson et al Transgenic animal models Models devoid of any disease- causing APP mutations Animal models expressing...

Ngày tải lên: 16/02/2014, 09:20

... V All reagents were supplied by Electron Microscopy Sciences (Hatfield, PA, USA) Assessement of SEC-isolated peptides by HPLC and SDS-PAGE Samples (100 lL) of peptides isolated by SEC were injected ... cost-effective than production of synthetic peptides, a bacterial expression system allows isotope labeling, which is essential for high-resolution structural analysis of Ab using NMR spectroscopy ... analysis and sequencing Amino acid analysis was performed at the Amino Acid Analysis Center, University of Uppsala, Sweden Sequence analysis was performed using an Applied Biosystems Procise 492...

Ngày tải lên: 18/02/2014, 13:20

... fluorescence We show the application of this assay to the testing of c-secretase inhibitors and PS1 mutants This assay allows for the first time the selection of cell populations and single cells ... assays based on APP or Notch c-secretase substrates can be used to specifically study modulation of c-secretase activity in parallel in various cell types Results of the inhibitor study suggest ... characterize c-secretase The advantage of this assay over existing systems is that it allows the isolation of cells with stable differences in c-secretase activity We established that the differences in...

Ngày tải lên: 08/03/2014, 08:20

... in transgenic mice, functional deficits and loss of synapses are, at least in some models, observed in young transgenic animals devoid of plaque deposits, suggesting that soluble Ab species are ... reflect disease severity Many types of oligomeric assemblies of Ab, with different structural characteristics, have been described and are suggested to contribute to the pathogenesis of AD [5] These ... these measures inversely correlated to escape latency at the last day of training (see Fig S2 ), suggesting that spatial search strategies were used by most of the animals Four individuals (two...

Ngày tải lên: 23/03/2014, 06:20

... Butyrylcholinesterase is also present in neurofibrillary tangles In Alzheimer s disease the expression of butyrylcholinesterase increases substantially in Alzheimer s disease patient s brain [47] ... present exclusively in the soluble fraction of an aggregating assay of Ab in a fibrillogenesis process [51] Moreover, using a probe that binds to low-molecular-mass isoforms of Ab it was observed ... from those of acetylcholinesterases in other tissues J Biol Chem 262, 4441–4444 10 Geula C & Mesulam M (1989) Special properties of cholinesterases in the cerebral cortex of Alzheimer s disease Brain...

Ngày tải lên: 23/03/2014, 07:20

... whereas a second, low-affinity binding site comprises residues 23–28 The results of these studies are discussed within the context of the general mechanism of the onset of pathologic states upon ... involvement of the histidines as metal ligands Asp1 shows a 0.60 residual signal intensity, whereas Val12 has a residual signal intensity of 0.52 ± 0.06 The signal reduction of Asp1 is equal to ... significant intensity losses, of > 80% The d-proton signals of His6 and His13 show some induced chemical shift changes, whereas His14 only exhibits intensity loss for the d-proton signal (Fig 2A)...

Ngày tải lên: 23/03/2014, 10:20

... secretion of APPsa was found to be enhanced significantly to A SH-SY5Y > 200% of control cells due to increased expression of the a-secretase ADAM10 This phenomenon was also seen in SKNMC cells although ... transport and function in late onset 5819 APLP2-shedding by disintegrin-metalloproteinases Alzheimer s disease Proc Natl Acad Sci USA 100, 2901–2905 47 Puchades M, Hansson SF, Nilsson CL, Andreasen ... other substrates such as cytokines [21], growth factors and their receptors [22,23], and adhesion molecules [24] If ADAMs have several cellular substrates, how are physiologically relevant processing...

Ngày tải lên: 30/03/2014, 11:20

... increased levels of cytokines in the brains of Alzheimer 's disease patients, and in transgenic mouse models of Alzheimer 's disease [10-12] However, all these reports have focused on a small number ... expressed in picograms per milligram of protein P < 0.05 was considered statistically significant Table 1: Quantification of Aβ levels in TgAPPsw and PS1/APPsw mouse brain slices Data expressed as ... review see [62]) Future studies will assess the relative proportions of monomers/dimers, oligomers or fibrils occurring in these mice brains and their relationship with the cytokine increases observed...

Ngày tải lên: 19/06/2014, 22:20

... Disorders and Stroke and the Alzheimer s disease and Related Disorders Association (NINCDS-ADRDA) [14] All AD cases were defined as sporadic because family histories showed no mention of first-degree ... all results Statistical analysis Hardy-Weinberg equilibrium was assessed using the Chi-square test Genotype and allele distributions were compared using the Chi-square test Differences in allele ... analyzed using a commercially available statistical package (SPSS Version 13.0, SPSS Inc., Chicago, IL) The criterion used for significant differences is P < 0.05 Results The alleles and genotypes frequencies...

Ngày tải lên: 19/06/2014, 22:20

... Karachi, consisting of 10 nodes Results and discussion Selection of docking protocol The selection of a valid docking protocol mainly focuses on the similarity of all redocked poses to the crystallographically ... cholinesterase inhibitors (ChEIs) is to increase the endogenous levels of acetylcholine (ACh) in the brains of AD patients, eventually increasing cholinergic neurotransmission It is not surprising ... pose was evaluated by considering the RMSDs values, docking scores and similarity scores The selected re-docked pose was further evaluated by its interactions and energetic analysis to investigate...

Ngày tải lên: 13/08/2014, 16:20

... hereditary diseases like Wilson s disease Huntington s disease is an involuntary movement disorder that is often associated with dementia Parkinson s disease is a progressive brain disorder and ... embarrassment, or single paraphasic expressions (milk pourer instead of cup) sometimes one observes that she is completely at a loss of words She clearly does not grasp some questions, and it seems ... feelings, vision problems, etc Degenerative diseases like Huntington s disease or other rare, usually genetically transmitted diseases may also cause dementia in adolescents This illness destroys...

Ngày tải lên: 14/02/2014, 18:20

... neurological, psychiatric and neuropsychological assessments were reviewed in a consensus conference comprised of neurologists, psychiatrists, and neuropsychologists Based on this review all participants ... It has been previously established that APOE variability is not associated with the rate of progression of Alzheimer s disease [51,59,67] The study was designed to address a specific question ... repetition of phrases from the Boston Diagnostic Aphasia Evaluation [19] Abstract reasoning was evaluated using WAIS-R Similarities subtest [66], and the non-verbal Identities and Oddities subtest of...

Ngày tải lên: 05/03/2014, 21:20

... ALZHEIMER S DISEASE AND RELATED DISORDERS This woman is a resident of a home for people with Alzheimer s disease Because of patients’ memory loss, signs have been posted as reminders of which flowers ... As the disease progresses, however, the entire library of memory closes down Memory loss is probably the most common sign associated with Alzheimer s disease In the initial stages of the disease, ... is essential in transmission of nerve impulses through the synapses of the brain and central nervous system (A synapse is the point at 33 LIFE OUT OF FOCUS: ALZHEIMER S DISEASE AND RELATED DISORDERS...

Ngày tải lên: 05/03/2014, 23:20

... as AD progresses Behavioral and personality changes, including agitation, aggression, and psychosis, often emerge as the disease progresses Depressed mood often occurs with AD Brain autopsies ... distinguish from Parkinson s disease, but the parkinsonism in DLB differs from Parkinson s disease by being more often symmetric, with less pronounced tremor (if any) Hallucinations are also ... Cognitive screening includes using validated screening instruments, such as the MMSE, and brief bedside assessments Cognitive screenings are usually sensitive to significant cognitive impairment associated...

Ngày tải lên: 05/03/2014, 23:20

... development is the result of an aberrant shift in activity of tau kinases and phosphatases [3] Thus, although targeting plaques and NFTs may ameliorate some of the consequences of AD and no doubt lessen ... is increased in cerebrospinal fluid in Alzheimer s disease but not Parkinson s disease Alzheimer Dis Assoc Disord 8, 190–197 Hye A, Lynham S, Thambisetty M, Causevic M, Campbell J, Byers HL, Hooper ... inhibition of synaptic transmission is dependent on the presence of Ab oligomers, and that Ab monomers are relatively nontoxic in these assays [56,57] As described above, synaptically released Zn is required...

Ngày tải lên: 07/03/2014, 10:20

... response This mechanism is based on the presence of lymphocytes in the mucosa of the nasal cavity and of the gastrointestinal tract This type of response produces primarily S- IgA antibodies but, ... 2007 The Authors Journal compilation ª 2007 FEBS 3785 Therapy for prion disease and AD T Wisniewski and E M Sigurdsson species Transmissibility of prionoses between different species is generally ... pathological b-sheet conformers is a key step in the pathogenesis of AD and prionoses, respectively In AD, these b-sheet rich structures consist of oligomers, protofibrils and fibrils that form plaques within...

Ngày tải lên: 07/03/2014, 10:20