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Cited by 120Adenosine and Purinergic SignalingPain Mechanisms and TreatmentsTraumatic Brain Injury and Neurovascular Disturbances

Purinergic Signalling and Neurological Diseases: An Update

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Burnstock, Geoffrey·2017·CNS & Neurological Disorders - Drug Targets
DOI 10.2174/1871527315666160922104848
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Abstract

Purinergic signalling, i.e. ATP as an extracellular signalling molecule and cotransmitter in both peripheral and central neurons, is involved in the physiology of neurotransmission and neuromodulation. Receptors for purines have been cloned and characterised, including 4 subtypes of the P1(adenosine) receptor family, 7 subtypes of the P2X ion channel nucleotide receptor family and 8 subtypes of the P2Y G protein-coupled nucleotide receptor family. The roles of purinergic signalling in diseases of the central nervous system and the potential use of purinergic compounds for their treatment are attracting increasing attention. In this review, the focus is on the findings reported in recent papers and reviews to update knowledge in this field about the involvement of purinergic signalling in Alzheimer's, Parkinson's and Huntington's diseases, multiple sclerosis, amyotrophic lateral sclerosis, degeneration and regeneration after brain injury, stroke, ischaemia, inflammation, migraine, epilepsy, psychiatric disorders, schizophrenia, bipolar disorder, autism, addiction, sleep disorders and brain tumours. The use in particular of P2X7 receptor antagonists for the treatment of neurodegenerative diseases, cancer, depression, stroke and ischaemia, A2A receptor antagonists for Parkinson's disease and agonists for brain injury and depression and P2X3 receptor antagonists for migraine and seizures has been recommended. P2Y receptors have also been claimed to be involved in some central nervous disorders.

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  • P2X7 receptor activation increases neuroinflammatory responses, which have been associated with neurodegenerative diseases, psychiatric disorders and stroke.

    “Remarkably, P2X7 receptor activation increases neuroinflammatory responses, which have been associated with neurodegenerative diseases, psychiatric disorders and stroke [21, 92–95], as further discussed.”

    From Hyperactivation of P2X7 receptors as a culprit of COVID-19 neuropathology (2021) · cites this paper as [94]

  • Purinergic signaling is involved in several psychiatric disorders, including MDD.

    “Purinergic signaling is involved in several psychiatric disorders, including MDD [25,26,27,28], and is mediated by nucleoside and nucleotide actions on P1 (P1R) and P2 (P2R) receptors.”

    From P2X7 Receptor Signaling in Stress and Depression (2019) · cites this paper as [27]

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Authors
Burnstock, G.
Affiliations
The Royal Free Hospital (GB)
Corresponding author
Burnstock, Geoffrey
ORCID
Burnstock, Geoffrey
Venue
CNS & Neurological Disorders - Drug Targets
Publisher
Bentham Science Publishers Ltd.
Published
2017-04-12
Volume
16
Issue
3
Pages
257-265
ISSN
  • 1568-007X (ISSN-L)
  • 1871-5273
DOI
10.2174/1871527315666160922104848
OpenAlex
W2527118361
Cited by
119
References
0
Citations by year
2026: 7 · 2025: 5 · 2024: 10 · 2023: 17 · 2022: 19 · 2021: 15 · 2020: 16 · 2019: 16 · 2018: 9 · 2017: 4 · 2013: 1
FWCI
9.45
Type
journal article
Language
en
Open access
Locations
  • CNS & Neurological Disorders - Drug Targets (publishedVersion)
  • PubMed (publishedVersion)
  • UCL Discovery (University College London) (submittedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Adenosine and Purinergic Signaling
  • Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
  • Health Sciences › Medicine › Neurology › Traumatic Brain Injury and Neurovascular Disturbances
Keywords
purinergic signaling, ATP as neurotransmitter, P2X7 receptor antagonists, adenosine A2A receptor antagonists, P2X3 receptor antagonist, neurodegenerative diseases, Alzheimer's disease, Parkinson's disease, Huntington's disease, multiple sclerosis, amyotrophic lateral sclerosis, brain injury, stroke, ischemia, migraine, epilepsy, mental illness, brain tumors
MeSH terms
Animals, Humans, Nervous System Diseases, Receptors, Purinergic, Signal Transduction, Purinergic P2X Receptor Antagonists

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