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

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出版社

SPRINGER BASEL AG
DOI: 10.1007/s00018-022-04185-6

关键词

Neuroserpin; Plasminogen; Tissue plasminogen activator; Glaucoma; Alzheimer's disease; Stroke; Serpin; Retina

资金

  1. CAUL
  2. National Health and Medical Research Council (NHMRC) of Australia
  3. Perpetual Hilcrest
  4. Ophthalmic Research Institute of Australia (ORIA)
  5. Macquarie University, NSW, Australia

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Neuroserpin is a crucial protein involved in neuronal development and various diseases, with mutations affecting its function and leading to pathological conditions. Understanding the alterations of neuroserpin and its cellular signaling networks is essential for studying its detrimental consequences and potential therapeutic targeting.
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.

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