Neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP) slows down Alzheimer's disease-like pathology in amyloid precursor protein-transgenic mice

Autor: Frank Tippmann, Clara Theunis, Falk Fahrenholz, Fred Van Leuven, Elzbieta Kojro, Ilse Dewachter, Ewa Wieczerzak, Dorothea Rat, Ulrich Schmitt, Rolf Postina
Přispěvatelé: UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire
Rok vydání: 2011
Předmět:
Genetically modified mouse
medicine.medical_specialty
endocrine system
G-protein-coupled receptor
factor-kappa-b
PAC1 receptor
pac1 receptor
Mice
Transgenic
Biology
g-protein-coupled receptor
Biochemistry
Research Communications
vasoactive-intestinal-peptide
Amyloid beta-Protein Precursor
Mice
Neurotrophic factors
Alzheimer Disease
Internal medicine
Genetics
Amyloid precursor protein
medicine
Animals
intranasal delivery
Receptor
neurotrophic factor
Molecular Biology
Neprilysin
long-term potentiation
Administration
Intranasal
nasal delivery
Brain
Long-term potentiation
gene-expression
Endocrinology
Alpha secretase
Gene Expression Regulation
alpha-secretase
biology.protein
Pituitary Adenylate Cyclase-Activating Polypeptide
central-nervous-system
neuroprotection
bdnf messenger-rna
neuronal cell-death
Somatostatin
hormones
hormone substitutes
and hormone antagonists
Biotechnology
Neurotrophin
Zdroj: The FASEB Journal
Article
FASEB journal : official publication of the Federation of American Societies for Experimental Biology, Vol. 25, no.9, p. 3208-18 (2011)
ISSN: 1530-6860
Popis: Pituitary adenylate cyclase-activating polypeptide (PACAP) has neuroprotective and neurotrophic properties and is a potent alpha-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 beta-peptide (A beta) transporter receptor for advanced glycation end products (RAGE) mRNA level. PACAP, by activation of the somatostatin-neprilysin cascade, also enhanced expression of the A beta-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.-Rat, D., Schmitt, U., Tippmann, F., Dewachter, I., Theunis, C., Wieczerzak, E, Postina, R., van Leuven, F., Fahrenholz, F., Kojro, E. Neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP) slows down Alzheimer's disease-like pathology in amyloid precursor protein-transgenic mice. FASEB J. 25, 3208-3218 (2011). www.fasebj.org ispartof: FASEB Journal vol:25 issue:9 pages:3208-3218 ispartof: location:United States status: published
Databáze: OpenAIRE
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