Affiliations: [a] Department of Molecular Pharmacology, Einstein Institute for Neuroimmunology and Inflammation, Albert Einstein College of Medicine, New York, NY, USA
| [b] Department of Medicine and Health Sciences, University of Molise, Campobasso, Italy
| [c] Casa di Cura “Montevergine”, Mercogliano (Avellino), Italy
| [d] Department of Mental and Physical Health and Preventive Medicine, University of Campania “Luigi Vanvitelli”, Naples, Italy
| [e] Department of Advanced Biomedical Sciences, University of Naples “Federico II”, Naples, Italy
| [f] Department of Medicine, Einstein Institute for Aging Research, Wilf Family Cardiovascular Research Institute, Albert Einstein College of Medicine, New York, NY, USA
Correspondence:
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Correspondence to: Gaetano Santulli, MD, PhD, FAHA, Albert Einstein College of Medicine, 1300 Morris Park Avenue, New York, NY 10461, USA. E-mail: gsantulli001@gmail.com.
Abstract: Alzheimer’s disease (AD) is a neurodegenerative disorder marked by amyloid-β accumulation, tau dysfunction, and neuroinflammation, involving endothelial cells and leukocytes. The breakdown of the blood-brain barrier allows immune cell infiltration, intensifying inflammation. A decreased ratio of Connexin-37 (Cx37, also known as GJA4: Gap Junction Protein Alpha 4) and Prolyl Hydroxylase Domain-Containing Protein 3 (PHD3, also known as EGLN3: Egl-9 Family Hypoxia Inducible Factor 3), Cx37/PHD3, consistently observed in different AD-related models, may represent a novel potential biomarker of AD, albeit the exact mechanisms underlying this phenomenon, most likely based on gap junction-mediated cellular interaction that modulate the cellular metabolite status, remain to be fully elucidated.
