Pathogenic chromatin modifiers: Their molecular action linking pathogenicity with genetic variability, epigenetic modifications and environmental factors in Alzheimer disease

• Published in: Bioscience hypotheses 2009-01, Vol.2 (3), p.163-169
• Main Author: Steinberg, M.G.
• Format: Article
• Language: English
• Subjects: Human immunodeficiency virus
• ISSN: 1756-2392
• DOI: 10.1016/j.bihy.2009.02.002

Most Alzheimer disease (AD) cases are unexplained. To identify causative agents for AD and to understand this chronic, complex disease process, the pathogenic chromatin modification hypothesis is put forward here, which links pathogenicity with genetic variability, epigenetic modifications and environmental factors. Host chromatin modification by pathogens (disease producers) directly exploiting susceptible genes of their hosts with DNA cleavage, and DNA, histone and other host chromatin protein modifications at defined sites, provide an understanding of the molecular mechanisms for the gene variation associations for AD and the effect of environmental and epigenetic factors. With the pathogenic chromatin modification hypothesis, the erratic success for AD pathogenicity of certain microbes is explained. If a microbe contains the pathogenic chromatin modifiers or their genes, and has the opportunity to infect a host, which has gene variants vulnerable to the pathogenic chromatin modifiers, then the disease process is initiated and promoted. This hypothesis postulates that pathogenic chromatin modifiers contribute to the DNA damage found in AD, and are tied to known risks including the [var epsilon]4 allele of apolipoprotein E, Down syndrome, the aging process and head injury. Restriction enzymes (REases) and methyltransferases (MTases), previously unrecognized as pathogens in AD or any disease, are a focus with specific suggestions for experiments to elucidate their possible role. The pathogenic chromatin modification hypothesis is relevant to other neurodegenerative disorders including human immunodeficiency virus (HIV) associated dementia and other chronic diseases. This work, integrating a multitude of genetic and environmental factors, presents new targets for therapeutic strategies.