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Acta Neurologica Belgica
Published in: Acta Neurologica Belgica 2/2024

Open Access 02-11-2023 | Tissue Plasminogen Activator | Review article

The probable role of tissue plasminogen activator/neuroserpin axis in Alzheimer’s disease: a new perspective

Authors: Naif H. Ali, Hayder M. Al-kuraishy, Ali I. Al-Gareeb, Saud A. Alnaaim, Athanasios Alexiou, Marios Papadakis, Hebatallah M. Saad, Gaber El-Saber Batiha

Published in: Acta Neurologica Belgica | Issue 2/2024

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Abstract

Alzheimer’s disease (AD) is the most common type of dementia associated with amyloid beta (Aβ) deposition. Dysfunction of the neuronal clearance pathway promotes the accumulation of Aβ. The plasminogen-activating system (PAS) is controlled by various enzymes like tissue plasminogen activators (tPA). Neuronal tPA enhances the conversion of plasminogen to plasmin, which cleaves Aβ; this function is controlled by many inhibitors of PAS, including a plasminogen-activating inhibitor (PAI-1) and neuroserpin. Therefore, the objective of the present narrative review was to explore the potential role of tPA/neuroserpin in the pathogenesis of AD. PAI-1 activity is increased in AD, which is involved in accumulating Aβ. Progressive increase of Aβ level during AD neuropathology is correlated with the over-production of PAI-1 with subsequent reduction of plasmin and tPA activities. Reducing plasmin and tPA activities promote Aβ by reducing Aβ clearance. Neuroserpin plays a critical role in the pathogenesis of AD as it regulates the expression and accumulation of Aβ. Higher expression of neuroserpin inhibits the neuroprotective tPA and the generation of plasmin with subsequent reduction in the clearance of Aβ. These observations raise conflicting evidence on whether neuroserpin is neuroprotective or involved in AD progression. Thus, neuroserpin over-expression with subsequent reduction of tPA may propagate AD neuropathology.

Graphical abstract

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Metadata
Title
The probable role of tissue plasminogen activator/neuroserpin axis in Alzheimer’s disease: a new perspective
Authors
Naif H. Ali
Hayder M. Al-kuraishy
Ali I. Al-Gareeb
Saud A. Alnaaim
Athanasios Alexiou
Marios Papadakis
Hebatallah M. Saad
Gaber El-Saber Batiha
Publication date
02-11-2023
Publisher
Springer International Publishing
Published in
Acta Neurologica Belgica / Issue 2/2024
Print ISSN: 0300-9009
Electronic ISSN: 2240-2993
DOI
https://doi.org/10.1007/s13760-023-02403-x

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