Physiological factors could enhance amyloid-beta toxicity

IV. A novel and simple fluorescence method for the measurement of presynaptic vesicular zinc release in acute hippocampal slices with a fluorescence plate reader. II. Membrane-lipid therapy in operation: the Hsp co-inducer BGP-15 activates stress signal transduction pathways by remodeling plasma membrane rafts. III. Hydroximic acid derivatives: pleiotrophic Hsp co-inducers restoring homeostasis and robustness. Abbreviations αSN Alpha-synuclein protein Aβ Amyloid-beta peptide ACSF Artificial cerebrospinal fluid AD Alzheimer " s disease ADDLs Aβ-derived diffusible ligands APP Amyloid precursor protein ASPD Native-amylospheroids BCA Bicinchoninic acid CDK5 Cyclin-dependent kinase 5 DLBD Diffuse Lewy body disease DMSO Dimethyl-sulfoxide DNP 2,4-dinitrophenol FBS Fetal bovine serum fEPSP Field excitatory postsynaptic potentials GSK-3β Glycogen synthase kinase 3 beta HEPES 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid LBD Lewy body diseases LBV Lewy body variant of Alzheimer " s disease LDH Lactate dehydrogenase LTP Long-term potentiation MAP Microtubule associated protein MEM Minimal essential medium NAC Non-amyloid component of Alzheimer " s disease amyloid NACP NAC precursor = alpha-synuclein NFTs Neurofibrillary tangles NMDA N-methyl-D-aspartate NMDAR N-methyl-D-aspartate receptor NR2B Subunit of NMDAR PBS Phosphate buffered saline PD Parkinson " s disease PI Propidium iodide PP-1 Protein phosphatase 1 PP-2A Protein phosphatase 2A RT Room temperature SDS-PAGE Sodium dodecyl sulphate-polyacrylamide gel electrophoresis SEM Standard error of mean TBS Theta-burst stimulation TEM Transmission electron microscopy upH 2 O MilliQ ultrapure water ZEN Zinc-enriched neuron ZnT Zinc transporter Alzheimer " s disease (AD) is a heterogeneous, progressive neurodegenerative disorder representing the most common cause of cognitive failure and dementia in older human patients. Extracellular deposition of beta amyloid peptide, intracellular formation of neurofibrillar tangles (NFT) caused by hyperphosphorylated tau protein and oxidative stress induced by impaired metabolic pathways and metals are the hallmarks of the disease primary theory for the cause of AD is the overproduction and/or impaired clearance of amyloid-beta (Aβ) peptides derived from amyloid precursor protein (APP), especially the The secondary hypothesis is the " metal hypothesis " which proposes the interaction of Aβ with specific metal ions that could enhance Aβ aggregation, pathogenicity and finally cause Brain tissues of AD patients after autopsy contain two main characteristic lesions: extracellular amyloid plaques and intracellular neurofibrillary tangles which are formed by hyperphosphorylated tau protein (Goedert and Crowther, 1989, Selkoe, 2003). There are two main forms of amyloid depositions: senile (or neuritic) and diffuse plaques. Senile plaques (originally observed by Alois Alzheimer) are extracellular spherical structures around 50–200 µm in diameter which contain a central amyloid core enriched …