The Nodding syndrome cerebrospinal fluid proteome: a lens into neurodevelopmental failure consistent with environmentally triggered MECP2 dysregulation?
These convergent molecular and clinical signatures suggest that NS may involve aberrant regulation of <i>MECP2</i>-associated networks. We propose a provisional model in which NS represents an environmentally induced functional phenocopy of <i>MECP2</i> network dysregulation, shaped by early-life immune and epigenetic perturbations and amplified by postnatal environmental stressors. Although direct epigenetic data and detailed exposure histories are currently limited, this integrative framework provides a testable model linking proteomic alterations and clinical observations to neurodevelopmental and immune-metabolic mechanisms, offering tractable directions for future mechanistic and therapeutic inquiry.
Authors
- Phillip A. Wilmarth (ORCID: https://orcid.org/0000-0002-7559-8727)
- Ashok P. Reddy (ORCID: https://orcid.org/0000-0003-1967-6927)
- Caesar Okot (ORCID: https://orcid.org/0000-0002-2312-5362)
- Raquel Valdes Angues (ORCID: https://orcid.org/0000-0003-2997-459X)
- Keith Zientek (ORCID: https://orcid.org/0000-0002-3601-3714)
- Valerie S. Palmer
- Peter S. Spencer
- Geoffrey Okello
- Ensio Ogal
- Alfred Lucid Blair Odong
- Lucy Kipwola Abwola
Institutions
- Oregon Health & Science University (US)
- United General Hospital (US)
- Skyworks Solutions (United States) (US)
Publication Details
- Journal
- Frontiers in Molecular Neuroscience
- Published
- 2026-01-29
- DOI
- https://doi.org/10.3389/fnmol.2026.1717920
- Primary Topic
- Genetics and Neurodevelopmental Disorders
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Oregon Health and Science University
- Uganda National Council for Science and Technology
- National Institutes of Health
- National Institute of Neurological Disorders and Stroke