We’re pleased to announce another update to our flagship Variant Report, the second this month! This update adds SNPs from a new gene, PRNP, to relevant sections of the Variant Report. Below you’ll find a brief summary of the PRNP gene compiled by Cynthia Smith of Nutrigenomics Wellness. As usual we’ll be updating existing v2.10 reports shortly.

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PRNP Major Prion Protein

  • The PRNP gene encodes a major prion protein, which likely plays a role in neuronal development and synaptic plasticity.

    • Neuronal development refers to the process of generating, developing, reshaping the nervous system from human embryo development, to death.

    • Synaptic plasticity refers to the ability of synapses in the brain to weaken or strengthen over time. Synaptic plasticity is one of the important neurochemical foundations of memory and learning.

  • PRNP may be required for neuronal myelin sheath maintenance. May promote myelin homeostasis through acting as an agonist for ADGRG6 receptor.

    • ADGRG6 – G-protein coupled receptor which is activated by type IV collagen, a major constituent of the basement membrane

  • PRNP may play a role in iron uptake and iron homeostasis.

  • A methionine/valine (M/V) polymorphism (SNP) at codon location 129 of the PRNP genetic sequence, represents a known risk factor for Creutzfeldt–Jakob disease (CJD)

  • Prion diseases also share similarities with additional neurodegenerative diseases, including Alzheimer’s disease (AD) or other types of dementia. AD and prion diseases were both verified as age-related diseases with possible genetic causative factors.

  • Early onset Alzheimer’s disease has been associated with a known PRNP mutation referred to as Val180Ile (c.G538A).

  • A very interesting research paper discusses emerging evidence that PRNP displays antimicrobial activity thereby inhibiting the replication of multiple viruses, and also interacts directly with Alzheimer’s disease (AD) amyloid-β (Aβ) peptide whose own antimicrobial role is now increasingly secure.

    • For years (and millions of dollars spent on rinse/repeat research) it was thought that the amyloid-β (Aβ) in AD brain might cause the disease, but emerging evidence argues that Aβ is an antimicrobial defense peptide induced in response to one or more viral infections. This raises the prospect that AD might be associated with brain infection.

    • This opens the possibility that PRNP may also be a component of the innate immune system.

      • PRNP resembles a large and diverse group of evolutionary ancient proteins that predate our adaptive immune system.

      • These ancient proteins are referred to as antimicrobial peptides.

    • PRNP expression is up-regulated by viral infections such as HIV-1, vesicular stomatitis virus and murine leukemia virus, HSV-1, adenovirus 5, hepatitis C virus, Coxsackievirus B3, Epstein–Barr virus, and Mycobacterium bovis.

      • There is direct evidence that PRNP plays a direct protective role in defense against virus infection

        • NOTE: It is now known that HSV-1 deploys an ‘anti-PRNP’ strategy

  • https://content.iospress.com/articles/journal-of-alzheimers-disease-reports/adr170037