Biliverdin Reductase-A Mediates the Beneficial Effects of Intranasal Insulin in Alzheimer Disease.
Administration, Intranasal
Aging
/ pathology
Alzheimer Disease
/ drug therapy
Animals
Behavior, Animal
Biomarkers
/ metabolism
Cell Line
Depression
/ complications
Hippocampus
/ drug effects
Insulin
/ administration & dosage
Insulin Receptor Substrate Proteins
/ metabolism
Insulin Resistance
Long-Term Potentiation
/ drug effects
Male
Memory
Memory Disorders
/ complications
Mice, Transgenic
Oxidative Stress
/ drug effects
Oxidoreductases Acting on CH-CH Group Donors
/ metabolism
Phenotype
Signal Transduction
/ drug effects
Alzheimer disease
Biliverdin reductase-A
Insulin resistance
Intranasal
Neuroprotection
Journal
Molecular neurobiology
ISSN: 1559-1182
Titre abrégé: Mol Neurobiol
Pays: United States
ID NLM: 8900963
Informations de publication
Date de publication:
Apr 2019
Apr 2019
Historique:
received:
01
05
2018
accepted:
10
07
2018
pubmed:
4
8
2018
medline:
7
8
2019
entrez:
4
8
2018
Statut:
ppublish
Résumé
Impairment of biliverdin reductase-A (BVR-A) is an early event leading to brain insulin resistance in AD. Intranasal insulin (INI) administration is under evaluation as a strategy to alleviate brain insulin resistance; however, the molecular mechanisms underlying INI beneficial effects are still unclear. We show that INI improves insulin signaling activation in the hippocampus and cortex of adult and aged 3×Tg-AD mice by ameliorating BVR-A activation. These changes were associated with a reduction of nitrosative stress, Tau phosphorylation, and Aβ oligomers in brain, along with improved cognitive functions. The role of BVR-A was strengthened by showing that cells lacking BVR-A: (i) develop insulin resistance if treated with insulin and (ii) can be recovered from insulin resistance only if treated with a BVR-A-mimetic peptide. These novel findings shed light on the mechanisms underlying INI treatment effects and suggest BVR-A as potential therapeutic target to prevent brain insulin resistance in AD.
Identifiants
pubmed: 30073505
doi: 10.1007/s12035-018-1231-5
pii: 10.1007/s12035-018-1231-5
doi:
Substances chimiques
Biomarkers
0
Insulin
0
Insulin Receptor Substrate Proteins
0
Irs1 protein, mouse
0
Oxidoreductases Acting on CH-CH Group Donors
EC 1.3.-
biliverdin reductase
EC 1.3.1.24
Types de publication
Journal Article
Langues
eng
Pagination
2922-2943Subventions
Organisme : Sapienza Università di Roma
ID : C26H15JT9X
Organisme : FP7 People: Marie-Curie Actions
ID : 624341
Organisme : Banca d'Italia
ID : 12868/17
Organisme : Ministero dell'Istruzione, dell'Università e della Ricerca
ID : RBSI144MT
Organisme : Ministero dell'Istruzione, dell'Università e della Ricerca
ID : 20153NBRS3_003
Organisme : Alzheimer's Association
ID : NIRG-14-321307
Pays : United States
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