Roles of Alpha-1 Antitrypsin in Human Health and Disease Models: 2nd Edition

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Molecular Medicine".

Deadline for manuscript submissions: 31 January 2027 | Viewed by 129

Editor


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Guest Editor
Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, FL, USA
Interests: functions and applications of alpha 1 antitrypsin (AAT) and SERPIN; development of novel treatment for autoimmune and inflammatory diseases; gene therapy using recombinant adeno-associated viral vectors (rAAV)
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Special Issue Information

Dear Colleagues,

Following a very successful first run, we are pleased to announce the launch of a second edition of a Special Issue on the roles of alpha-1 antitrypsin in human health and disease models. 

Alpha-1 antitrypsin (AAT), a member of serine proteinase inhibitor (SERPIN) superfamily, has multiple functions including the inhibition of proteinases and the regulation of immune system. As a proteinase inhibitor, AAT can reduce tissue damage and degeneration, which is commonly involved in autoimmune and inflammatory diseases. AAT can also interact with immune regulatory molecules and mediate anti-inflammatory effects. Studies have shown that AAT has the therapeutic potential for the treatment of human diseases including AAT deficiency (AATD), graft-versus-host disease (GvHD), type 1 diabetes (T1D), systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and COVID-19. However, the mechanism(s) underlying the therapeutic effects of AAT remain elusive. In addition, AAT may have unknown functions to be further investigated. This Specific Issue aims to publish recent findings that advance the therapeutic applications and the functional mechanism(s) of AAT and related molecules.

Prof. Dr. Sihong Song
Guest Editor

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Keywords

  • alpha-1 antitrypsin
  • serine proteinase inhibitor (SERPIN)
  • autoimmunity
  • inflammation
  • aging
  • cancer

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Published Papers (1 paper)

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Research

21 pages, 2006 KB  
Article
Human α1-Antitrypsin Inhibits Nociceptor Excitability and Relieves Inflammatory and Neuropathic Pain
by Alaina L. Waters, Santiago Loya-López, Erick J. Rodriguez-Palma, Shainnel O. Eans, Ryosuke Shinouchi, Jordan Stokes, Jay P. McLaughlin, Sihong Song and Rajesh Khanna
Biomolecules 2026, 16(8), 1074; https://doi.org/10.3390/biom16081074 - 23 Jul 2026
Abstract
Chronic pain affects hundreds of millions of people and remains poorly managed, as the most effective drugs, including opioids, carry side effects that limit long-term use. Because inflammation drives both the initiation and maintenance of chronic pain, anti-inflammatory mechanisms are an attractive analgesic [...] Read more.
Chronic pain affects hundreds of millions of people and remains poorly managed, as the most effective drugs, including opioids, carry side effects that limit long-term use. Because inflammation drives both the initiation and maintenance of chronic pain, anti-inflammatory mechanisms are an attractive analgesic target. We investigated human alpha-1 antitrypsin (hAAT), a serine proteinase inhibitor with potent anti-inflammatory activity and established protection across disease models, as a candidate analgesic, using Aralast NP®, a clinical-grade, already-approved formulation that makes findings directly translatable. Using calcium imaging and patch-clamp electrophysiology in mouse dorsal root ganglion (DRG) neurons, we found that hAAT reduced activation of low-voltage-activated Ca2+ channels and dampened intrinsic excitability. Veratridine-evoked Ca2+ responses, a sodium-channel-dependent readout of nociceptor activity, were suppressed by hAAT to a degree comparable to the selective sodium channel inhibitors ProTx-II (NaV1.7) and VX-548 (NaV1.8), driven by loss of the nociceptor-associated response profiles. In vivo, hAAT decreased pain sensitivity and pain-associated behaviors in both inflammatory and neuropathic models. Together, these findings reveal a mechanism by which hAAT suppresses nociceptor activity and position Aralast NP® as a safe, effective candidate for treating chronic pain. Full article
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