المؤلفون: Annamalai Prakasam, Chitra Venugopal, Anitha Suram, Kumar Sambamurti

المصدر: Current Alzheimer Research. 3:365-375

مصطلحات موضوعية: Amyloid, Tau protein, Apoptosis, Inflammation, Proteomics, medicine.disease_cause, Alzheimer Disease, medicine, Animals, Humans, Senile plaques, Amyloid beta-Peptides, biology, Neurodegeneration, Brain, medicine.disease, Genes, cdc, Oxidative Stress, Neurology, Biochemistry, Mutation, biology.protein, Neurology (clinical), Tumor Suppressor Protein p53, Alzheimer's disease, medicine.symptom, Oxidative stress, DNA Damage, Signal Transduction

الوصف: Alzheimer's disease (AD) is a complex neurodegenerative disorder pathologically identified by the presence of extracellular senile plaques (SP) with a proteinaceous core composed of aggregates of the amyloid peptide (Abeta) and intracellular aggregates of the microtubule-associated protein tau (tau) as neurofibrillary tangles (NFTs). These hallmarks consist of abnormally folded proteinaceous components that are believed to be neurotoxic in AD. The mechanisms of toxicity remain unclear although oxidative stress and inflammation are implicated as mediators of the toxicity and these lesions, in turn, are known to damage cellular components including proteins, lipids in the membrane and DNA. However effects on genotoxicity and its role in AD are less clear. The present review discusses various influences, in particular of amyloid, on the genetic material and their possible role in the neurodegeneration in AD. Further, the amalgamation of genomics and proteomics in understanding AD and therapeutic development is suggested.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::eec7c5a2134dd2af78c34753085dec9dTest
https://doi.org/10.2174/156720506778249380Test

المؤلفون: Nigel H. Greig, Debomoy K. Lahiri, Kumar Sambamurti, Chitra Venugopal, Yan Zhou, Annamalai Prakasam, Anitha Suram

المصدر: Current Alzheimer Research. 3:81-90

مصطلحات موضوعية: Amyloid, Microtubule-associated protein, Neurodegeneration, P3 peptide, Membrane Proteins, Biology, medicine.disease, Biochemistry of Alzheimer's disease, Neurology, Membrane protein, Alzheimer Disease, Endopeptidases, Nerve Degeneration, Presenilin-1, medicine, Amyloid precursor protein, biology.protein, Animals, Aspartic Acid Endopeptidases, Humans, Neurology (clinical), Amyloid Precursor Protein Secretases, Alzheimer's disease, Neuroscience

الوصف: The amyloid hypothesis has dominated the thinking in our attempts to understand, diagnose and develop drugs for Alzheimer's disease (AD). This article presents a new hypothesis that takes into account the numerous familial AD (FAD) mutations in the amyloid precursor protein (APP) and its processing pathways, but suggests a new perspective beyond toxicity of forms of the amyloid beta-peptide (Abeta). Clearly, amyloid deposits are an invariable feature of AD. Moreover, although APP is normally processed to secreted and membrane-bound fragments, sAPPbeta and CTFbeta, by BACE, and the latter is subsequently processed by gamma-secretase to Abeta and CTFgamma, this pathway mostly yields Abeta of 40 residues, and increases in the levels of the amyloidogenic 42-residue Abeta (Abeta42) are seen in the majority of the mutations linked to the disease. The resulting theory is that the disease is caused by amyloid toxicity, which impairs memory and triggers deposition of the microtubule associated protein, Tau, as neurofibrillary tangles. Nevertheless, a few exceptional FAD mutations and the presence of large amounts of amyloid deposits in a group of cognitively normal elderly patients suggest that the disease process is more complex. Indeed, it has been hard to demonstrate the toxicity of Abeta42 and the actual target has been shifted to small oligomers of the peptide, named Abeta derived diffusible ligands (ADDLs). Our hypothesis is that the disease is more complex and caused by a failure of APP metabolism or clearance, which simultaneously affects several other membrane proteins. Thus, a traffic jam is created by failure of important pathways such as gamma-secretase processing of residual intramembrane domains released from the metabolism of multiple membrane proteins, which ultimately leads to a multiple system failure. In this theory, toxicity of Abeta42 will only contribute partially, if at all, to neurodegeneration in AD. More significantly, this theory would predict that focussing on specific reagents such as gamma-secretase inhibitors that hamper metabolism of APP, may initially show some beneficial effects on cognitive performance by elimination of acutely toxic ADDLs, but over the longer term may exacerbate the disease process by reducing membrane protein turnover.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::306d0ea352b0b2ee6eed81e937eef792Test
https://doi.org/10.2174/156720506775697142Test

المؤلفون: Nigel H. Greig, Lawrence T. Friedhoff, Edward I. Cullen, Debomoy K. Lahiri, Gosse Bruinsma, Kumar Sambamurti

المصدر: Alzheimer's & Dementia. 2

مصطلحات موضوعية: Oral treatment, medicine.medical_specialty, Amyloid, Epidemiology, business.industry, Health Policy, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Endocrinology, Developmental Neuroscience, Internal medicine, medicine, Neurology (clinical), Geriatrics and Gerontology, Presentation (obstetrics), Beta (finance), business

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::abf853584dd2db6d2ec1842d74dd60c6Test
https://doi.org/10.1016/j.jalz.2006.05.379Test

المؤلفون: Nigel H. Greig, George M. Alley, Kumar Sambamurti, Jason A. Bailey, Debomoy K. Lahiri, Demao Chen

المصدر: Neurobiology of Aging. 25:S63-S64

مصطلحات موضوعية: Aging, biology, Amyloid, business.industry, General Neuroscience, Memantine, Disease, Pharmacology, medicine, biology.protein, Neurology (clinical), Geriatrics and Gerontology, business, Developmental Biology, medicine.drug, Cholinesterase

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::bde4146a96ac30b7d57a39f9b8fbe24aTest
https://doi.org/10.1016/s0197-4580Test(04)80214-8