Herpes simplex virus type 1 contributes to Alzheimer’s disease by preventing regulation of formation and destruction of Aβ amyloid plaques.
Introduction. Over 25 million people in the world are affected by dementia, most suffering from Alzheimer’s Disease (AD), a progressive neurodegenerative disease caused by an accumulation of Aβ amyloid3. However, what triggers this Aβ accumulation has yet to be clearly defined. In this commentary, herpes simplex virus type 1 (HSV-1) will be explored as a possible trigger of Aβ production. Aβ is classified as an antimicrobial peptide produced to protect neurons from infections, since neurons are self-limited and will not be replaced if they undergo apoptosis. 1 Aβ oligomers have been shown to inhibit HSV-1 infection in vitro.1 HSV-1 inhibits the destruction of Aβ oligomers produced by innate immunity, by inhibiting lysosomal and autophagic processes.5 Proving HSV-1 stimulation and dysregulation of Aβ would provide new possible treatment options for AD. Methods. Transgenic mice were given the human Aβ gene and infected with HSV-1. The WT and transgenic mice were compared without HSV-1 present, with HSV-1 present initially, and 21 days post infection with anti-Aβ antibodies, Aβ binding ELISA, immunofluorescence labeling, and TEM analysis of HSV-1, Aβ proteins, and Aβ amyloid plaques. 1 Results. In WT mice, no Aβ was present with or without HSV-1 present, and post infection. In the transgenic mice Aβ was minimally present without HSV-1, highly prevalent in HSV-1 infection, and 21 days post infection HSV-1, Aβ proteins, and Aβ amyloid plaques were all present, and in the same areas. Other studies have shown HSV-1 surface glycoproteins seem to impair endosomal trafficking, including the fusion of lysosomes with autophagosomes,2 as well as, specific HSV-1 proteins phosphorylate eIF2α and interfere with autophagy upregulation.6 Conclusions. These results indicate that HSV-1 does trigger the production of Aβ proteins and Aβ amyloid plaques as part of an immune response to infection and by inhibiting Aβ recycling. This research indicates a possible new target to treat AD by targeting upregulation of autophagy to break down the Aβ oligomers before they form plaques. Lithium is a drug currently on that market that upregulates autophagy4 and can easily cross the blood brain barrier. This commentary explores the potential of lithium as a possible treatment for AD.
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