El CRAI romandrà tancat del 24 de desembre de 2025 al 6 de gener de 2026. La validació de documents es reprendrà a partir del 7 de gener de 2026.
El CRAI permanecerá cerrado del 24 de diciembre de 2025 al 6 de enero de 2026. La validación de documentos se reanudará a partir del 7 de enero de 2026.
From 2025-12-24 to 2026-01-06, the CRAI remain closed and the documents will be validated from 2026-01-07.
 
Miniatura

Fitxers

731316.pdf (2.8 MB)

Tipus de document

Article

Versió

Versió publicada

Data de publicació

2022-01-28

Llicència de publicació

cc-by (c) Solés Tarrés, Irene et al., 2022
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/194329

Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) Protects Striatal Cells and Improves Motor Function in Huntington's Disease Models: Role of PAC1 Receptor.

Títol de la revista

Autors

Director/Tutor

ISSN de la revista

Títol del volum

Recurs relacionat

https://doi.org/10.3389/fphar.2021.797541

Resum

Huntington's disease (HD) is a hereditary neurodegenerative disorder caused by the expression of mutant huntingtin (mHtt). One of the main features of HD is the degeneration of the striatum that leads to motor discoordination. Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide that acts through three receptors named PAC1R, VPAC1R, and VPAC2R. In the present study, we first investigated the effect of PACAP on STHdhQ7/Q7 and STHdhQ111/Q111 cells that express wild-type Htt with 7 and mHtt with 111 glutamines, respectively. Then we explored the capacity of PACAP to rescue motor symptoms in the R6/1, a murine model of HD. We found that PACAP treatment (10-7 M) for 24 h protects STHdhQ111/Q111 cells from mHtt-induced apoptosis. This effect is associated with an increase in PAC1R transcription, phosphorylation of ERK and Akt, and an increase of intracellular c-fos, egr1, CBP, and BDNF protein content. Moreover, the use of pharmacological inhibitors revealed that activation of ERK and Akt mediates these antiapoptotic and neurotrophic effects of PACAP. To find out PAC1R implication, we treated STHdh cells with vasoactive intestinal peptide (VIP), which exhibits equal affinity for VPAC1R and VPAC2R, but lower affinity for PAC1R, in contrast to PACAP which has same affinity for the three receptors. VIP reduced cleaved caspase-3 protein level, without promoting the expression of c-fos, egr1, CBP, and the neurotrophin BDNF. We next measured the protein level of PACAP receptors in the striatum and cortex of R6/1 mice. We observed a specific reduction of PAC1R at the onset of motor symptoms. Importantly, the intranasal administration of PACAP to R6/1 animals restored the motor function and increased the striatal levels of PAC1R, CBP, and BDNF. In conclusion, PACAP exerts antiapoptotic and neurotrophic effects in striatal neurons mainly through PAC1R. This effect in HD striatum allows the recovery of motor function and point out PAC1R as a therapeutic target for treatment of HD.

Matèries

Corea de Huntington, Malalties neurodegeneratives, Malalties del sistema nerviós, Receptors neurals

Matèries (anglès)

Huntington's chorea, Neurodegenerative Diseases, Nervous system Diseases, Neural receptor

Citació

Col·leccions

Articles publicats en revistes (Biomedicina)
Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)
Articles publicats en revistes (Institut de Neurociències (UBNeuro))

Citació

SOLÉS TARRÉS, Irene, CABEZAS LLOBET, Núria, LEFRANC, Benjamin, LEPRINCE, Jérôme, ALBERCH I VIÉ, Jordi, VAUDRY, David, XIFRÓ I COLLSAMATA, Xavier. Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) Protects Striatal Cells and Improves Motor Function in Huntington's Disease Models: Role of PAC1 Receptor.. _Frontiers in Pharmacology_. 2022. Vol. 12, núm. 797541. [consulta: 1 de gener de 2026]. ISSN: 1663-9812. [Disponible a: https://hdl.handle.net/2445/194329]

Exportar metadades

JSON - METS

Compartir registre