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Pathogenic or protective? Neuropeptide Y in amyotrophic lateral sclerosis

Clark, CM, Clark, RM ORCID: 0000-0001-6156-6671, Hoyle, JA and Dickson, TC ORCID: 0000-0002-9196-1661 2021 , 'Pathogenic or protective? Neuropeptide Y in amyotrophic lateral sclerosis' , Journal of Neurochemistry, vol. 156, no. 3 , pp. 273-289 , doi: 10.1111/jnc.15125.

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Abstract

Neuropeptide Y (NPY) is an endogenous peptide of the central and enteric nervous systems which has gained significant interest as a potential neuroprotective agent for treatment of neurodegenerative disease. Amyotrophic lateral sclerosis (ALS) is an aggressive and fatal neurodegenerative disease characterized by motor deficits and motor neuron loss. In ALS, recent evidence from ALS patients and animal models has indicated that NPY may have a role in the disease pathogenesis. Increased NPY levels were found to correlate with disease progression in ALS patients. Similarly, NPY expression is increased in the motor cortex of ALS mice by end stages of the disease. Although the functional consequence of increased NPY levels in ALS is currently unknown, NPY has been shown to exert a diverse range of neuroprotective roles in other neurodegenerative diseases; through modulation of potassium channel activity, increased production of neurotrophins, inhibition of endoplasmic reticulum stress and autophagy, reduction of excitotoxicity, oxidative stress, neuroinflammation and hyperexcitability. Several of these mechanisms and signalling pathways are heavily implicated in the pathogenesis of ALS. Therefore, in this review, we discuss possible effects of NPY and NPY-receptor signalling in the ALS disease context, as determining NPY's contribution to, or impact on, ALS disease mechanisms will be essential for future studies investigating the NPY system as a therapeutic strategy in this devastating disease.

Item Type: Article
Authors/Creators:Clark, CM and Clark, RM and Hoyle, JA and Dickson, TC
Keywords: amyotrophic lateral sclerosis, interneurons, neurodegeneration, neuropeptide Y, neuroprotection
Journal or Publication Title: Journal of Neurochemistry
Publisher: Raven Press
ISSN: 0022-3042
DOI / ID Number: 10.1111/jnc.15125
Copyright Information:

© 2020 International Society for Neurochemistry

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