ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2011
Neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP) slows down Alzheimer's disease-like pathology in amyloid precursor protein-transgenic mice.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers, 1 of them a synthesis that pooled it.
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Who cites it
88 citing papers in PubMed, 1 synthesis or guideline pooled it, 143 citations in OpenAlex.
- Meta-Analysis of Transcriptomic Studies of Blood and Six Brain Regions Identifies a Consensus of 15 Cross-Tissue Mechanisms in Alzheimer's Disease and Suggests an Origin of Cross-Study Heterogeneity.American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics · 2025Pooled it
- Impaired peptide amidation and risk of incident dementia in the Malmoe preventive project cohort.Alzheimer's research & therapy · 2026Article
- Low Brain Levels of Dietary Polyphenols and Their Conjugates: Reassessing Mechanisms of Alzheimer's Disease Prevention.Journal of dementia and alzheimer's disease · 2026Article
- Neuropeptides in the Management of Alzheimer's Disease: From Pathophysiology to Therapeutic Opportunities.International journal of molecular sciences · 2026Review
- Moderate Exercise Stimulates PACAP-Mediated Neurogenesis in Rat Dentate Gyrus and Cerebellar Cortex.Journal of functional morphology and kinesiology · 2026Article
- Crossing Barriers: Advancements in Macromolecular Therapeutics for Neurodegenerative Diseases and Strategies to Overcome the Blood-Brain Barrier.ACS pharmacology & translational science · 2025Review
- More Than Three Decades After Discovery of the Neuroprotective Effect of PACAP, What Is Still Preventing Its Clinical Use?Journal of molecular neuroscience : MN · 2025Review
- Microbial dipeptidyl peptidases of the S9B family as host-microbe isozymes.Science advances · 2025Review
- Deconvolution Analysis of G and F-Actin Unfolding: Insights into the Thermal Stability and Structural Modifications Induced by PACAP.International journal of molecular sciences · 2025Article
- Enhancing Stability and Bioavailability of Peptidylglycine Alpha-Amidating Monooxygenase in Circulation for Clinical Use.Biomolecules · 2025Article
- Anorexigenic neuropeptides as anti-obesity and neuroprotective agents: exploring the neuroprotective effects of anorexigenic neuropeptides.Bioscience reports · 2024Review
- Pituitary adenylyl cyclase-activating polypeptide modulates the stress response: the involvement of different brain areas and microglia.Frontiers in psychiatry · 2024Review
- Nose-to-Brain (N2B) Delivery: An Alternative Route for the Delivery of Biologics in the Management and Treatment of Central Nervous System Disorders.Pharmaceutics · 2023Review
- Alterations in pituitary adenylate cyclase-activating polypeptide in major depressive disorder, bipolar disorder, and comorbid depression in Alzheimer's disease in the human hypothalamus and prefrontal cortex.Psychological medicine · 2023Article
- Recent Uses of Lipid Nanoparticles, Cell-Penetrating and Bioactive Peptides for the Development of Brain-Targeted Nanomedicines against Neurodegenerative Disorders.Nanomaterials (Basel, Switzerland) · 2023Review
- Review
- PACAP-Sirtuin3 alleviates cognitive impairment through autophagy in Alzheimer's disease.Alzheimer's research & therapy · 2023Article
- The Potential of the Nose-to-Brain Delivery of PACAP for the Treatment of Neuronal Disease.Pharmaceutics · 2023Review
- Clinical evidence of human pathogens implicated in Alzheimer's disease pathology and the therapeutic efficacy of antimicrobials: an overview.Translational neurodegeneration · 2023Review
- Alternative Pharmacological Strategies for the Treatment of Alzheimer's Disease: Focus on Neuromodulator Function.Biomedicines · 2022Review
28 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pituitary adenylate cyclase-activating polypeptide (PACAP) has neuroprotective and neurotrophic properties and is a potent α-secretase activator. As PACAP peptides and their specific receptor PAC1 are localized in central nervous system areas affected by Alzheimer's disease (AD), this study aims to examine the role of the natural peptide PACAP as a valuable approach in AD therapy. We investigated the effect of PACAP in the brain of an AD transgenic mouse model. The long-term intranasal daily PACAP application stimulated the nonamyloidogenic processing of amyloid precursor protein (APP) and increased expression of the brain-derived neurotrophic factor and of the antiapoptotic Bcl-2 protein. In addition, it caused a strong reduction of the amyloid β-peptide (Aβ) transporter receptor for advanced glycation end products (RAGE) mRNA level. PACAP, by activation of the somatostatin-neprilysin cascade, also enhanced expression of the Aβ-degrading enzyme neprilysin in the mouse brain. Furthermore, daily PAC1-receptor activation via PACAP resulted in an increased mRNA level of both the PAC1 receptor and its ligand PACAP. Our behavioral studies showed that long-term PACAP treatment of APP[V717I]-transgenic mice improved cognitive function in animals. Thus, nasal application of PACAP was effective, and our results indicate that PACAP could be of therapeutic value in treating AD.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.