Potential Crosstalk Between the PACAP/VIP Neuropeptide System and Endoplasmic Reticulum Stress-Relevance to Multiple Sclerosis Pathophysiology

Overview

Journal Cells

Publisher MDPI

Specialties Biochemistry
Biophysics
Cell Biology
Molecular Biology

Date 2023 Nov 24

PMID 37998368

Authors

Minduli Withana

Alessandro Castorina

Affiliations

Soon will be listed here.

Abstract

Multiple sclerosis (MS) is an immune-mediated disorder characterized by focal demyelination and chronic inflammation of the central nervous system (CNS). Although the exact etiology is unclear, mounting evidence indicates that endoplasmic reticulum (ER) stress represents a key event in disease pathogenesis. Pituitary adenylate cyclase-activating peptide (PACAP) and vasoactive intestinal peptide (VIP) are two structurally related neuropeptides that are abundant in the CNS and are known to exert neuroprotective and immune modulatory roles. Activation of this endogenous neuropeptide system may interfere with ER stress processes to promote glial cell survival and myelin self-repair. However, the potential crosstalk between the PACAP/VIP system and ER stress remains elusive. In this review, we aim to discuss how these peptides ameliorate ER stress in the CNS, with a focus on MS pathology. Our goal is to emphasize the importance of this potential interaction to aid in the identification of novel therapeutic targets for the treatment of MS and other demyelinating disorders.

Citing Articles

Pituitary adenylyl cyclase-activating polypeptide modulates the stress response: the involvement of different brain areas and microglia.

Singh A, Shim P, Naeem S, Rahman S, Lutfy K Front Psychiatry. 2025; 15:1495598.

PMID: 39931196 PMC: 11807976. DOI: 10.3389/fpsyt.2024.1495598.

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