Neuroserpin, a crucial regulator for axogenesis, synaptic modelling and cell–cell interactions in the pathophysiology of neurological disease

Angela Godinez, Rashi Rajput, Nitin Chitranshi*, Veer Gupta, Devaraj Basavarajappa, Samridhi Sharma, Yuyi You, Kanishka Pushpitha, Kunal Dhiman, Mehdi Mirzaei, Stuart Graham, Vivek Gupta

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

13 Citations (Scopus)
67 Downloads (Pure)

Abstract

Neuroserpin is an axonally secreted serpin that is involved in regulating plasminogen and its enzyme activators, such as tissue plasminogen activator (tPA). The protein has been increasingly shown to play key roles in neuronal development, plasticity, maturation and synaptic refinement. The proteinase inhibitor may function both independently and through tPA-dependent mechanisms. Herein, we discuss the recent evidence regarding the role of neuroserpin in healthy and diseased conditions and highlight the participation of the serpin in various cellular signalling pathways. Several polymorphisms and mutations have also been identified in the protein that may affect the serpin conformation, leading to polymer formation and its intracellular accumulation. The current understanding of the involvement of neuroserpin in Alzheimer’s disease, cancer, glaucoma, stroke, neuropsychiatric disorders and familial encephalopathy with neuroserpin inclusion bodies (FENIB) is presented. To truly understand the detrimental consequences of neuroserpin dysfunction and the effective therapeutic targeting of this molecule in pathological conditions, a cross-disciplinary understanding of neuroserpin alterations and its cellular signaling networks is essential.

Original languageEnglish
Article number172
Pages (from-to)1-23
Number of pages23
JournalCellular and Molecular Life Sciences
Volume79
Issue number3
DOIs
Publication statusPublished - 4 Mar 2022

Bibliographical note

Copyright the Author(s) 2022. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

Keywords

  • Alzheimer’s disease
  • Glaucoma
  • Neuroserpin
  • Plasminogen
  • Retina
  • Serpin
  • Stroke
  • Tissue plasminogen activator

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