Pathogenic Mechanisms of the Arctic Alzheimer Mutation
نویسنده
چکیده
The Arctic mutation interferes with processing of the amyloid precursor protein. The Arctic Alzheimer mutation favors intracellular Aȕ production by making APP less available to Į-secretase. Journal of Neurochemistry, in press.ȕ oligomers are inefficiently measured by enzyme-linked immunosorbent assay. and Johansson AS. Docosahexaenoic acid stimulates non-amyloidogenic APP processing resulting in reduced Aȕ levels in cell models of Alzheimer's disease. Manuscript. Reprints were made with permission from the publishers. Abbreviations AA Arachidonic acid ĮAPPs Alfa-APP soluble Aȕ Amyloid-ȕ AD Alzheimer's disease ADAM A disintegrin and metalloprotease ADDL Aȕ-derived diffusible ligands AICD APP intracellular domain APH-1 Anterior pharynx defective-1 ApoE Apolipoprotein E APP Amyloid precursor protein BACE Beta-site APP-cleaving enzyme ȕAPPs Beta-APP soluble CAA Cerebral amyloid angiopathy CSF Cerebrospinal fluid DHA Docosahexaenoic acid DMEM Dulbecco's modified eagle medium ELISA Enzyme-linked immunosorbent assay ER Endoplasmic reticulum HEK Human embryonic kidney HPLC High-performance liquid chromatography HRP Horseradish peroxidase IDE Insulin degrading enzyme IP Immunoprecipitation NICD Notch intracellular domain NMDA N-methyl-D-aspartate PAGE Polyacrylamide gel electrophoresis PEN-2 Presenilin enhancer-2 PS Presenilin RP-HPLC Reverse-phase high-performance liquid chromatography SDS Sodium dodecyl sulfate SEC-HPLC Size exclusion chromatography high-performance liquid chromatography 11
منابع مشابه
Clinical and neuropathological features of the arctic APP gene mutation causing early-onset Alzheimer disease.
BACKGROUND A majority of mutations within the beta-amyloid region of the amyloid precursor protein (APP) gene cause inherited forms of intracerebral hemorrhage. Most of these mutations may also cause cognitive impairment, but the Arctic APP mutation is the only known intra-beta-amyloid mutation to date causing the more typical clinical picture of Alzheimer disease. OBJECTIVE To describe featu...
متن کاملAlzheimer ’s Disease: Possible Mechanisms Behind Neurohormesis Induced by Exposure to Low Doses of Ionizing Radiation
In 2016, scientists reported that human exposure to low doses of ionizing radiation (CT scans of the brain) might relieve symptoms of both Alzheimer’s disease (AD) and Parkinson disease (PD). The findings were unbelievable for those who were not familiar with neurohormesis. X-ray stimulation of the patient’s adaptive protection systems against neurodegenerative diseases was the mechanism pr...
متن کاملInsights into Alzheimer disease pathogenesis from studies in transgenic animal models
Alzheimer disease is the most common cause of dementia among the elderly, accounting for ~60-70% of all cases of dementia. The neuropathological hallmarks of Alzheimer disease are senile plaques (mainly containing p-amyloid peptide derived from amyloid precursor protein) and neurofibrillary tangles (containing hyperphosphorylated Tau protein), along with neuronal loss. At present there is no ef...
متن کاملScreening of DFNB3 in Iranian families with autosomal recessive non-syndromic hearing loss reveals a novel pathogenic mutation in the MyTh4 domain of the MYO15A gene in a linked family
Objective(s): Non-syndromic sensorineural hearing loss (NSHL) is a common disorder affecting approximately 1 in 500 newborns. This type of hearing loss is extremely heterogeneous and includes over 100 loci. Mutations in the GJB2 gene have been implicated in about half of autosomal recessive NSHL (ARNSHL) cases, making this the most common cause of ARNSHL. For the latter form of deafness, most f...
متن کاملExpandable DNA Repeat and Human Hereditary Disorders
Background & Aims: Nearly 30 hereditary disorders in humans result from an increase in the number of copies of simple repeats in genomic DNA, including fragile X syndrome, myotonic dystrophy, Huntington’s disease, and Friedreich’s ataxia. One the most frequently occurring types of mutation is trinucleotide repeat expansion. The present study was conducted with the aim of investigating the cause...
متن کامل