Herpes simplex virus type 1 and Alzheimer's disease: the autophagy connection.
The causes of Alzheimer's disease (AD) and of the characteristic pathological features - amyloid plaques and neurofibrillary tangles - of AD brain are unknown, despite the enormous resources provided over the years for their investigation. Indeed, the only generally accepted risk factors are age, Down syndrome, carriage of the type 4 allele of the apolipoprotein E gene (APOE-epsilon 4), and possibly brain injury. Following the authors' previous studies implicating herpes simplex virus type 1 (HSV1) in brain of APOE-epsilon 4 carriers as a major cause of AD, the authors propose here, on the basis of their and others' recent studies, that not only does HSV1 generate the main components of amyloid plaques and neurofibrillary tangles (NFTs) - beta-amyloid (A beta) and abnormally phosphorylated tau but also, by disrupting autophagy, it prevents degradation of these aberrant proteins, leading to their accumulation and deposition, and eventually to AD.
Itzhaki
Ruth F
RF
Faculty of Life Sciences, The University of Manchester, Manchester, UK. ruth.itzhaki@manchester.ac.uk
Cosby
S Louise
SL
Wozniak
Matthew A
MA
D000367:Age Factors; D000368:Aged; D000544:Alzheimer Disease / Q000209:etiology / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D053327:Apolipoprotein E4 / Q000235:genetics; D001343:Autophagy; D001921:Brain / Q000821:virology; D020803:Encephalitis, Herpes Simplex / Q000150:complications / Q000821:virology; D015852:Eukaryotic Initiation Factor-2 / Q000378:metabolism; D020022:Genetic Predisposition to Disease; D018259:Herpesvirus 1, Human / Q000302:isolation & purification / Q000472:pathogenicity*; D006801:Humans; D008247:Lysosomes / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010766:Phosphorylation; D058225:Plaque, Amyloid / Q000378:metabolism / Q000473:pathology; D014176:Protein Biosynthesis; D011499:Protein Processing, Post-Translational; D014764:Viral Proteins / Q000502:physiology; D019892:eIF-2 Kinase / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism
D016229:Amyloid beta-Peptides; D053327:Apolipoprotein E4; D015852:Eukaryotic Initiation Factor-2; C054369:MAPT protein, human; D009419:Nerve Tissue Proteins; D014764:Viral Proteins; C066469:gamma 34.5 protein, Human herpesvirus 1; D016875:tau Proteins; D019892:eIF-2 Kinase