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Protective Agents in Parkinson’s Disease: Caffeine and Adenosine A2A Receptor Antagonists

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Handbook of Neurotoxicity

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Abstract

Based on several findings suggesting that the adenosinergic system is one of the most interesting in the field of neuroprotection in Parkinson’s disease, this chapter describes the functions of the purine adenosine and its A2A receptors in the central nervous system, with emphasis on their role in neuroprotection. The neuromodulatory role of A2A receptors and the preclinical and epidemiological studies on the mechanisms of the neuroprotective role of caffeine and urate, the final product of purine catabolism, are extensively discussed in the light of their potential modifying effects on Parkinson’s disease.

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Abbreviations

5-HT1A:

Serotonin receptors type-1A

6-OHDA:

6-Hydroxydopamine

AD:

Alzheimer’s disease

ALS:

Amyotrophic lateral sclerosis

AMP:

Adenosine monophosphate

ATP:

Adenosine triphosphate

BG:

Basal ganglia

CB1:

Cannabinoid receptors type-1

CNS:

Central Nervous System

CPS:

Cancer Prevention Study

CPu:

Caudate-putamen nucleus

CSC:

8-(−3-Chlorostyryl) caffeine

DA:

Dopamine

GABA:

γ-Aminobutyric acid

GABAergic:

γ-Aminobutyric acidergic

GPe:

External portion of globus pallidus

GPi:

Internal portion of globus pallidus

HD:

Huntington’s disease

HHP:

Honolulu Heart Program

HPFS:

Health Professionals Follow-Up Study

L-DOPA:

L-3,4-Dihydroxyphenylalanine

mGLU4:

Metabotropic glutamate receptors type-4

mGLU5:

Metabotropic glutamate receptors type-5

MPEP:

2-Methyl-6-(phenylethynyl)pyridine

MPP+:

1-Methyl-4-phenylpyridinium

MPTP:

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

NHS:

Nurses’ Health Study

NIH:

National Institutes of Health

NMDA:

N-Methyl-D-aspartate

PD:

Parkinson’s disease

SNc:

Substantia nigra pars compacta

SNr:

Substantia nigra pars reticulata

STN:

Subthalamic nucleus

TH:

Tyrosine hydroxylase

UPDRS:

Unified Parkinson’s Disease Rating Scale

ZM 241385:

4-(2-[7-amino-2-(2-furyl)[1,2,4]triazolo[2,3-a][1,3,5]triazin-5-ylamino]ethyl)phenol

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Acknowledgments

This study was supported by funds from MIUR (Ministero dell’Istruzione, dell’Università e della Ricerca PRIN 2017 (Pr. 2017LYTE9M, PI Prof. Micaela Morelli).

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Authors and Affiliations

  1. Department of Biomedical Sciences, University of Cagliari, Cagliari, Italy

    Nicola Simola, Annalisa Pinna, Lucia Frau, Giulia Costa, Jacopo Marongiu, Pathik Parekh, Marcello Serra & Micaela Morelli

  2. CNR Institute of Neuroscience, Cagliari, Italy

    Annalisa Pinna & Micaela Morelli

Authors
  1. Nicola Simola
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  2. Annalisa Pinna
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  3. Lucia Frau
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  4. Giulia Costa
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  7. Marcello Serra
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Correspondence to Micaela Morelli .

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  1. Department of Biomedical Sciences, East Tennessee State University, Johnson City, TN, USA

    Richard M. Kostrzewa

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Simola, N. et al. (2021). Protective Agents in Parkinson’s Disease: Caffeine and Adenosine A2A Receptor Antagonists. In: Kostrzewa, R.M. (eds) Handbook of Neurotoxicity. Springer, Cham. https://doi.org/10.1007/978-3-030-71519-9_103-1

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  • DOI: https://doi.org/10.1007/978-3-030-71519-9_103-1

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