The Role of Progranulin (PGRN) in the Pathogenesis of Ischemic Stroke

© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature..

Stroke is a life-threatening medical condition and is a leading cause of disability. Cerebral ischemia is characterized by a distinct inflammatory response starting with the production of various cytokines and other inflammation-related agents. Progranulin (PGRN), a multifunctional protein, is critical in diverse physiological reactions, such as cell proliferation, inflammation, wound healing, and nervous system development. A mature PGRN is anti-inflammatory, while granulin, its derivative, conversely induces pro-inflammatory cytokine expression. PGRN is significantly involved in the brain tissue and its damage, for example, improving mood and cognitive disorders caused by cerebral ischemia. It may also have protective effects against nerve and spinal cord injuries by inhibiting neuroinflammatory response and apoptosis or it may be related to the proliferation, accumulation, differentiation, and activation of microglia. PGRN is a neurotrophic factor in the central nervous system. It may increase post-stroke neurogenesis of the subventricular zone (SVZ), which is particularly important in improving long-term brain function following cerebral ischemia. The neurogenesis enhanced via PGRN in the ischemic brain SVZ may be attributed to the induction of PI3K/AKT and MAPK/ERK signaling routes. PGRN can also promote the proliferation of neural stem/progenitor cells through PI3K/AKT signaling pathway. PGRN increases hippocampal neurogenesis, reducing anxiety and impaired spatial learning post-cerebral ischemia. PGRN alleviates cerebral ischemia/reperfusion injury by reducing endoplasmic reticulum stress and suppressing the NF-κB signaling pathway. PGRN can be introduced as a potent neuroprotective agent capable of improving post-ischemia neuronal actions, mainly by reducing and elevating the inflammatory and anti-inflammatory cytokines. Expression, storage, cleavage, and function of progranulin (PGRN) in the pathogenesis of ischemic stroke.

Medienart:

E-Artikel

Erscheinungsjahr:

2023

Erschienen:

2023

Enthalten in:

Zur Gesamtaufnahme - volume:43

Enthalten in:

Cellular and molecular neurobiology - 43(2023), 7 vom: 10. Okt., Seite 3435-3447

Sprache:

Englisch

Beteiligte Personen:

Purrahman, Daryush [VerfasserIn]
Shojaeian, Ali [VerfasserIn]
Poniatowski, Łukasz A [VerfasserIn]
Piechowski-Jóźwiak, Bartłomiej [VerfasserIn]
Mahmoudian-Sani, Mohammad-Reza [VerfasserIn]

Links:

Volltext

Themen:

Cerebral ischemia
Cytokines
EC 2.7.1.-
EC 2.7.11.1
Inflammation
Journal Article
Neuroprotection
Phosphatidylinositol 3-Kinases
Progranulin
Progranulins
Proto-Oncogene Proteins c-akt
Review
Stroke

Anmerkungen:

Date Completed 05.09.2023

Date Revised 05.09.2023

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1007/s10571-023-01396-8

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM360609309