UPS-mediated P-glycoprotein regulation in Alzheimer's disease: pharmacological implications for the amyloid pathology.

Authors

Aditi Joshi, Jotiram Salunkhe, Vinod Ugale

Published in

Molecular biology reports. Volume 53. Issue 1. Sep 07, 2026. Epub Sep 07, 2026.

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disorder marked by the accumulation of amyloid β (Aβ), tau pathology, neuroinflammation, oxidative stress, and neurovascular dysfunction. Growing evidence suggests that impaired clearance of Aβ across the blood-brain barrier (BBB), rather than overproduction alone, is a key factor driving progression of AD. P-glycoprotein (P-gp) plays a crucial role in Aβ removal and is consistently reduced in AD. This review focuses on the mechanisms underlying P-gp dysfunction, particularly its regulation by the ubiquitin-proteasome system. Herein, we have discussed multiple factors associated with the AD, such as Aβ, oxidative stress, and inflammatory signaling, contributing to the phosphorylation, ubiquitination, internalization, and degradation of P-gp. These processes result in impaired transporter function and a compromised integrity of the BBB. The review further examines experimental and clinical evidence linking altered P-gp turnover with defective Aβ clearance in AD.

PMID:
42704522
Bibliographic data and abstract were imported from PubMed on 08 Sep 2026.

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