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Emerging role of S100B protein implication in Parkinson’s disease pathogenesis

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Abstract

The exact etiology of Parkinson’s disease (PD) remains obscure, lacking effective diagnostic and prognostic biomarkers. In search of novel molecular factors that may contribute to PD pathogenesis, emerging evidence highlights the multifunctional role of the calcium-binding protein S100B that is widely expressed in the brain and predominantly in astrocytes. Preclinical evidence points towards the possible time-specific contributing role of S100B in the pathogenesis of neurodegenerative disorders including PD, mainly by regulating neuroinflammation and dopamine metabolism. Although existing clinical evidence presents some contradictions, estimation of S100B in the serum and cerebrospinal fluid seems to hold a great promise as a potential PD biomarker, particularly regarding the severity of motor and non-motor PD symptoms. Furthermore, given the recent development of S100B inhibitors that are able to cross the blood brain barrier, novel opportunities are arising in the research field of PD therapeutics. In this review, we provide an update on recent advances in the implication of S100B protein in the pathogenesis of PD and discuss relevant studies investigating the biomarker potential of S100B in PD, aiming to shed more light on clinical targeting approaches related to this incurable disorder.

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Abbreviations

PD:

Parkinson’s disease

SNpc:

Substantia nigra pars compacta

MPTP:

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine

6-OHDA:

6-Hydroxydopamine

GDNF:

Glial-derived neurotrophic factor

BBB:

Blood–brain barrier

DAMP:

Damage-associated molecular pattern

RAGE:

Receptor for advanced glycation end products

HMGB1:

High mobility group box 1

LIMK:

LIM kinase

AP-1:

Activating protein-1

COX-2:

Cyclooxygenase-2

TNF-α:

Tumor necrosis factor- α

CNS:

Central nervous system

ROS:

Reactive oxygen species

cAMP:

Cyclic adenosine monophosphate

ERKs:

Extracellular signal-regulated kinases

GRK2:

G protein-coupled receptor kinase 2

DBS:

Deep brain stimulation

SNP:

Single-nucleotide polymorphism

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Acknowledgements

YNP would like to acknowledge Monash University Malaysia for supporting with HDR Scholarship.

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This research has not received any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Authors and Affiliations

  1. Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 75 M. Asias Street, 11527, Athens, Greece

    Efthalia Angelopoulou & Christina Piperi

  2. Neuropharmacology Research Laboratory, Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Bandar Sunway, Selangor, Malaysia

    Yam Nath Paudel

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  1. Efthalia Angelopoulou
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  2. Yam Nath Paudel
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  3. Christina Piperi
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EA carried out the literature review, conceptualized, and prepared the initial draft. YNP edited and contributed in the final manuscript. CP provided critical inputs, edited and contributed to the final version of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Christina Piperi.

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Angelopoulou, E., Paudel, Y.N. & Piperi, C. Emerging role of S100B protein implication in Parkinson’s disease pathogenesis. Cell. Mol. Life Sci. 78, 1445–1453 (2021). https://doi.org/10.1007/s00018-020-03673-x

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