Incretin and insulin signaling as novel therapeutic targets for Alzheimer’s and Parkinson’s disease

Nowell, Joseph; Blunt, Eleanor; Edison, Paul

doi:10.1038/s41380-022-01792-4

Cited by 136Alzheimer's disease research and treatmentsNeuroinflammation and Neurodegeneration MechanismsParkinson's Disease Mechanisms and Treatments

Incretin and insulin signaling as novel therapeutic targets for Alzheimer’s and Parkinson’s disease

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Nowell, Joseph, Blunt, Eleanor, Edison, Paul·2023·Molecular Psychiatry

DOI 10.1038/s41380-022-01792-4PMC PMC9812772

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Abstract

Despite an ever-growing prevalence and increasing economic burden of Alzheimer’s disease (AD) and Parkinson’s disease (PD), recent advances in drug development have only resulted in minimally effective treatment. In AD, along with amyloid and tau phosphorylation, there is an associated increase in inflammation/glial activation, a decrease in synaptic function, an increase in astrocyte activation, and a state of insulin resistance. In PD, along with α-synuclein accumulation, there is associated inflammation, synaptic dysfunction, dopaminergic neuronal loss, and some data to suggest insulin resistance. Therapeutic strategies for neurodegenerative disorders have commonly targeted individual pathological processes. An effective treatment might require either utilization of multiple drugs which target the individual pathological processes which underlie the neurodegenerative disease or the use of a single agent which could influence multiple pathological processes. Insulin and incretins are compounds with multiple effects on neurodegenerative processes. Preclinical studies have demonstrated that GLP-1 receptor agonists reduce neuroinflammation, reduce tau phosphorylation, reduce amyloid deposition, increase synaptic function, and improve memory formation. Incretin mimetics may act through the restoration of insulin signaling pathways, inducing further neuroprotective effects. Currently, phase 2 and phase 3 trials are underway in AD and PD populations. Here, we provide a comprehensive review of the therapeutic potential of incretin mimetics and insulin in AD and PD.

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GLP-1R agonists have neuroprotective effects in PD, attributed to restoring insulin signaling, reducing glial activation, neuroinflammation, and oxidative stress.
“The neuroprotective effects of GLP-1R agonists in PD are supported in numerous preclinical studies and have been attributed to their ability to restore insulin signaling, reduce glial activation, neuroinflammation, and oxidative stress.”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [395]

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Authors: Nowell, J., Blunt, E., & Edison, P.
Affiliations: Imperial College London (GB)
Corresponding author: Edison, Paul
ORCID: Blunt, Eleanor
Edison, Paul
Venue: Molecular Psychiatry
Publisher: Springer Science and Business Media LLC
Published: 2022-10-18
Volume: 28
Issue: 1
Pages: 217-229
ISSN: 1359-4184 (ISSN-L)
1476-5578
DOI: 10.1038/s41380-022-01792-4
PMC: PMC9812772
OpenAlex: W4306685147
Cited by: 136
References: 161
Citations by year: 2026: 32 · 2025: 43 · 2024: 43 · 2023: 18
FWCI: 3.58
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0 (tdm)
creativecommons.org/licenses/by/4.0 (vor)
Locations: Molecular Psychiatry (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
ORCA Online Research @Cardiff (Cardiff University) (acceptedVersion)
Topics: Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
Keywords: Alzheimer's disease, Parkinson's disease, incretins, insulin signaling, GLP-1 receptor agonists, incretin mimetics, insulin resistance, neuroinflammation, tau phosphorylation, amyloid deposition, synaptic dysfunction, neuroprotection, therapeutic target
MeSH terms: Alzheimer Disease, Humans, Inflammation, Insulin, Insulin Resistance, Parkinson Disease, Neurodegenerative Diseases, Incretins

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Incretin and insulin signaling as novel therapeutic targets for Alzheimer’s and Parkinson’s disease

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