Age-Related Undercarboxylated-Osteocalcin Loss May Heighten Dopaminergic Vulnerability to α-Synuclein Pathology in Parkinson's Disease

Authors

Kacia Huang · Katelyn Huang · Nahed Bdewi · Pokfah Nuwong · Raahimah Ghani

Brighton College Abu Dhabi, Abu Dhabi, United Arab Emirates

Abstract

Parkinson's disease (PD) is now widely recognised not only as a brain-specific disorder but as a systemic failure of organ-to-organ communication. Evidence suggests that the osteo-neural axis may have an effect on neuronal vulnerability, indicating that bone-derived hormones can modulate PD risk. This study investigates whether undercarboxylated osteocalcin (ucOCN), a hormone produced by osteoblasts in the bone, directly protects dopaminergic (DA) neurons from α-synuclein (α-syn)-induced structural degeneration. Using SH-SY5Y cell lines, primary DA neuron cultures, and mouse models, we examined how different ucOCN concentrations affect neurite integrity following α-syn exposure. Our predicted findings show that higher ucOCN levels preserve DA neurite structure, supporting the concept of a bone-brain axis in PD. These projected results suggest that age-related ucOCN decline may increase neuronal susceptibility and identify ucOCN as a potential biomarker and therapeutic target.

Keywords: Parkinson's disease, osteocalcin, dopaminergic neuron, α-synuclein, bone-brain axis

Contact the Authors

Kacia Huang — kaciahuangsy@gmail.com

Katelyn Huang — katelynhuangsq@gmail.com

Pokfah Nuwong — npokfah@gmail.com

Raahimah Ghani — raahimahghani@gmail.com