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Cited by 180Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

Brain insulin resistance: role in neurodegenerative disease and potential for targeting

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Hölscher, Christian·2020·Expert Opinion on Investigational Drugs
DOI 10.1080/13543784.2020.1738383
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Abstract

Introduction: This review evaluates the novel strategy of treating Alzheimer’s and Parkinson’s disease (AD and PD) withdrugs that initially have been developed to treat type 2 diabetes. As insulin signalling has been found to be de-sensitized in the brains of patients, drugs that can re-sensitize insulin signalling have been tested to evaluate if this strategy can alter disease progression.Areas covered: The review will give an overview of preclinical and clinical tests in AD and PD of drugs activating insulin receptors, glucagon-like peptide -1 (GLP-1) receptors, and glucose-dependent insulinotropic polypeptide (GIP) receptors.Expert opinion: Insulin, GLP-1 and GIP receptor agonists have shown good effects in preclinical studies. First clinical trials in MCI/AD patients have shown that insulin can improve on key pathological symptoms of AD such as memory impairment, brain activity, neuronal energy utilization, and inflammation markers. A GLP-1 receptor agonist has shown disease-modifying effects in PD patients, and first pilot studies have shown encouraging effects of a GLP-1 receptor agonist in AD patients. Novel dual GLP-1/GIP receptor agonists that cross the blood brain barrier show superior neuroprotective effects compared to single GLP-1 or GIP receptor agonists, and show great promise as novel treatments of AD and PD.

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Cited by

Sorted by citations

Authors
Hölscher, C.
Affiliations
Henan University of Chinese Medicine (CN)
Corresponding author
Hölscher, Christian
ORCID
Hölscher, Christian
Venue
Expert Opinion on Investigational Drugs
Publisher
Informa UK Limited
Published
2020-03-16
Volume
29
Issue
4
Pages
333-348
ISSN
  • 1354-3784 (ISSN-L)
  • 1744-7658
DOI
10.1080/13543784.2020.1738383
OpenAlex
W3012083507
Cited by
180
References
23
Citations by year
2026: 24 · 2025: 30 · 2024: 29 · 2023: 18 · 2022: 34 · 2021: 30 · 2020: 15
FWCI
3.09
Type
journal article
Language
en
Open access
Licence
Locations
  • Expert Opinion on Investigational Drugs (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
brain insulin resistance, Alzheimer's disease, Parkinson's disease, GLP-1 receptor agonists, GIP receptor agonist, GIP/GLP-1 receptor agonist, neurodegeneration, neuroprotection, blood-brain barrier, disease-modifying therapy, mild cognitive impairment
MeSH terms
Glucagon-Like Peptide-1 Receptor, Glucagon-Like Peptide-1 Receptor Agonists, Alzheimer Disease, Animals, Brain, Gastric Inhibitory Polypeptide, Humans, Insulin, Insulin Resistance, Parkinson Disease, Receptors, Gastrointestinal Hormone, Glucagon-Like Peptide 1

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