and gene based therapies for parkinson s disease

... social sciences It is essential to promote the understanding of this formidable disease and to share new findings among researchers in the field Clinical and basic research of Alzheimer s disease ... in presenilins (PSs) and bAPP genes [6] It has been proposed that PS, as functions of these genes, are proteolytic enzymes (␥-secretases) and ␤APP is thought to be one of their substrates [7], ... drebrin, that also shows severe loss in AD Fish Oil and n–3 Fatty Acids As discussed above, DHA is enriched in synapses and DHA is reduced in diets associated with AD risk DHA levels in AD brain are...

Ngày tải lên: 14/02/2014, 17:20

... 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 significant The levels of APC showed much less variation ... level for APC in differentiating cases from controls Comparisons of the follow-up samples were performed with Friedman 's test, followed by Dunn 's test for posthoc comparisons when appropriate SPSS ... proportions of patients between the two groups when appropriate Spearman 's rank correlation was used for assessing correlations Receiver operating characteristics analysis was used for determination...

Ngày tải lên: 12/08/2014, 23:21

... membranes To complement our MC99-3FLAG based in vitro c-secretase assays, an in vitro assay using COS7SPC99-3FLAG CHAPSO extracts was developed The substrate in this assay is synthesized, processed, ... 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...

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 ... 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, ... rt-PCR reverse-transcriptase-Polymerase Chain Reaction S1 P Sphingosine-1-Phosphate S1 PL S1 P-lyase S1 PR - S1 P Receptor - sAPP soluble APP SDS Sodiumdodecylsulfate SDS-PAGE Sodiumdodecylsulfate Polyacrylamide...

Ngày tải lên: 25/11/2015, 15:23

... microtubule-associated protein that normally serves to assemble and stabilize microtubules Genetics and risk factors implicated in Alzheimer s disease pathogenesis Familial forms of AD, with an autosomal ... and cortical vessels with few diffuse plaques, severe loss of SMCs, weakening of vessel walls leading to hemorrhage and perivascular microgliosis and astrocytosis The Dutch and Iowa mutations ... assemblies of Ab trigger aggregation of tau and the formation of NFTs, but also inflammation and oxidative stress, by rather unclear mechanisms These downstream processes give rise to progressive...

Ngày tải lên: 16/02/2014, 09:20

... of synthetic peptides, a bacterial expression system allows isotope labeling, which is essential for high-resolution structural analysis of Ab using NMR spectroscopy and allows use of high specific ... gels (A,C) and 1% agarose gels (B,D), and proteins were visualized by Coomassie stain Lanes HS and LS are molecular mass standards, with the molecular mass in kDa given on the left (E) 1% agarose ... Analysis Center, University of Uppsala, Sweden Sequence analysis was performed using an Applied Biosystems Procise 492 cLC sequenator (Applied Biosystems, Framingham, MA, USA) employing standard...

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 ... Francisco, CA, USA) Results Assay design This novel c-secretase assay involves cotransfection of a substrate-activator and a reporter gene into mammalian cells, as outlined in Fig 1A The substrate-activator ... COS-7 and CHO cells resulted in the expression of GFP positive cells Figure 1B shows phase (panels and 3) and fluorescence microscopy (panels and 4) of COS-7 cells transfected with both constructs...

Ngày tải lên: 08/03/2014, 08:20

... ¨ was used as horseradish peroxidase substrate and the reaction was stopped with m H2SO4 Wells were washed three times between each step after blocking the plates and antibodies and samples were ... models and human disease, it is still interesting and important to reflect upon these observations and to try to provide explanations A comparison between APP transgenic models and the human disease ... aberrations in synapse composition, shape, and density provide a molecular basis for loss of connectivity in Alzheimer s disease J Neurosci 27, 796–807 Cleary JP, Walsh DM, Hofmeister JJ, Shankar...

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] ... acetylcholinesterase associated with senile plaques differs from the enzyme found in normal fibers and neurons with respect to optimal pH, inhibition by excess substrate and protease inhibitor sensitivity ... Butyrylcholinesterase shares many structural and physicochemical properties with acetylcholinesterase [49] Therefore, butyrylcholinesterase was evaluated as a possible molecular chaperone for amyloid formation...

Ngày tải lên: 23/03/2014, 07:20

... residues and 15 also show a signal intensity decrease, but not as prominent as for the others Crosspeaks for residues 1, 6, 13 and 14 are not visible even with no copper added As well as the selective ... His13, His14 and Asp1 as ligands The binding seems to be specific and affects mainly the ligands and the neighboring residues The detected residue-specific signal loss upon metal binding arises from ... respectively, show significant signal intensity losses All three histidines are affected In (A), it is shown that H6 and H13 show some induced shift but H14 only exhibits signal intensity loss for...

Ngày tải lên: 23/03/2014, 10:20

... M, Hansson SF, Nilsson CL, Andreasen N, Blennow K & Davidsson P (2003) Proteomic studies of potential cerebrospinal fluid protein markers for Alzheimer s disease Brain Res Mol Brain Res 118, 140–146 ... 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 to a lesser ... factors and their receptors [22,23], and adhesion molecules [24] If ADAMs have several cellular substrates, how are physiologically relevant processing events coordinated? One possibility is a...

Ngày tải lên: 30/03/2014, 11:20

... Alzheimer 's disease J Neurosci 2001, 21:372-81 Araujo DM, Lapchak PA: Induction of immune system mediators in the hippocampal formation in Alzheimer 's and Parkinson' s diseases: selective effects on specific ... interests 11 Authors' contributions NP carried out the in-vitro brain slice assays, processed brain tissues, performed the Bio-plex assay, ELISAs and drafted the manuscript DP conceived the design ... the study, carried out Bio-plex assays, performed statistical analyses and aided in manuscript preparation VM analyzed data and constructed dendrograms AQ aided in ELISA and Bio-plex assays and...

Ngày tải lên: 19/06/2014, 22:20

... 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 and ... AD; NINCDS-ADRDA: National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer s disease and Related Disorders Association; ORs: odds ratios; PCR: polymerase chain ... 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

... modeling steps Likewise, pose and pose as well as pose and pose have pair-wise RMSDs ≥ to 1.5 Å, but neither individual pose energies nor MolDock Score [Grid] values allowed these poses to be selected ... also guards access to the bottom of the cleft and adopts three major conformations; open, closed, and an intermediate access position [48] For cleft-spanning ligands such as DECA, Phe330 assumes ... progressive neurodegenerative disorder caused by the loss of neurons and synapses in the cerebral cortex and certain sub-cortical regions The main risk factor for AD is increased age: as people...

Ngày tải lên: 13/08/2014, 16:20

... 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 ... Psychological Disorders Alzheimer s Disease and Other Dementias Psychological Disorders Addiction Alzheimer s Disease and Other Dementias Anxiety Disorders Child Abuse and Stress Disorders Depression ... blood vessels that supply the heart muscle with oxygen and nutrients narrow These diseases can cause strokes and heart disease (heart attacks) in the elderly The most common causes of illness and...

Ngày tải lên: 14/02/2014, 18:20

... Information from the neurological, psychiatric and neuropsychological assessments were reviewed in a consensus conference comprised of neurologists, psychiatrists, and neuropsychologists Based ... 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 the ... skills remained stable Increased age was associated with lower scores in all cognitive domains while increased education was associated with higher scores APOE-␧4 was not associated with poor performance...

Ngày tải lên: 05/03/2014, 21:20

... dementia caused by medical conditions such as head injuries, diseases caused by the human immunodeficiency virus (HIV), Parkinson s disease, and Huntington s disease; and substance-induced persisting ... teenagers The second factor to consider is human memory Memory loss—one of the most obvious and distressing symptoms of Alzheimer s disease is much more serious than forgetting the answers on a history ... 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

... cognition and alertness, parkinsonism, and visual hallucinations DLB may be difficult to distinguish from Parkinson s disease, but the parkinsonism in DLB differs from Parkinson s disease by being ... deficits are prominent and become more severe and global as AD progresses Behavioral and personality changes, including agitation, aggression, and psychosis, often emerge as the disease progresses ... 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

... Identifying these mechanisms will substantially facilitate the development of more effective therapeutic strategies Metal dyshomeostasis and AD Transition metals such as Cu and Fe are essential for normal ... enzymes because activity of the enzymes is dependent on optimal metal loading Cu deficiency is central to the recessive Menkes and Wilson diseases, and has been implicated in AD Just as excess Cu ... stress The study by Busciglio et al [85] in this regard is of particular relevance These authors demonstrated that an increase in oxidative stress alters APP processing and generates an increase...

Ngày tải lên: 07/03/2014, 10:20

... Whether similar approaches can be used for prion disease remains to be determined Prion disease Interest in prion disease has greatly increased subsequent to the emergence of BSE in England and the ... fibrillizes and deposits as plaques within the brain This process is facilitated by various pathological chaperones as well as several metals The aim of most therapeutic interventions for these conformational ... is called ‘the species barrier’ Therefore, scrapie (a prionosis affecting sheep) is not transmissible to humans The species barrier does not provide absolute protection; therefore, transmission...

Ngày tải lên: 07/03/2014, 10:20