Astrocytes Expressing Vitamin D-activating Enzyme Identify Parkinson's Disease

Overview

Journal CNS Neurosci Ther

Specialties Neurology
Pharmacology

Date 2022 Feb 15

PMID 35166042

Authors

Samanta Mazzetti

Michela Barichella

Federica Giampietro

Angelica Giana

Alessandra M Calogero

Alida Amadeo

Nicola Palazzi

Alessandro Comincini

Giorgio Giaccone

Manuela Bramerio

Serena Caronni

Viviana Cereda

Emanuele Cereda

Graziella Cappelletti

Chiara Rolando

Gianni Pezzoli

Affiliations

Soon will be listed here.

Abstract

Introduction: Astrocytes are involved in Parkinson's disease (PD) where they could contribute to α-Synuclein pathology but also to neuroprotection via α-Synuclein clearance. The molecular signature underlying their dual role is still elusive. Given that vitamin D has been recently suggested to be protective in neurodegeneration, the aim of our study was to investigate astrocyte and neuron vitamin D pathway alterations and their correlation with α-Synuclein aggregates (ie, oligomers and fibrils) in human brain obtained from PD patients.

Methods: The expression of vitamin D pathway components CYP27B1, CYP24A1, and VDR was examined in brains obtained from PD patients (Braak stage 6; n = 9) and control subjects (n = 4). We also exploited proximity ligation assay to identified toxic α-Synuclein oligomers in human astrocytes.

Results: We found that vitamin D-activating enzyme CYP27B1 identified a subpopulation of astrocytes exclusively in PD patients. CYP27B1 positive astrocytes could display neuroprotective features as they sequester α-Synuclein oligomers and are associated with Lewy body negative neurons.

Conclusion: The presence of CYP27B1 astrocytes distinguishes PD patients and suggests their contribution to protect neurons and to ameliorate neuropathological traits.

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