Annexin A1 in neurological disorders: Neuroprotection and glial modulation

Author(s)

Ferreira, Luiz Philipe de Souza ; da Silva, Rafael Andre ; Borges, Pamela Pacassa ; Xavier, Luana Filippi ; Scharf, Pablo ; Sandri, Silvana ; Oliani, Sonia M. ; Farsky, Sandra H. P. ; Gil, Cristiane D.

• Document type: Journal article
• Source: PHARMACOLOGY & THERAPEUTICS; v. 267, p. 10-pg., 2025-03-01.

Abstract

Neurological disorders, such as neurodegenerative and neuroinflammatory diseases, have contributed significantly to global disability, even considering the rising life years expectations. Therefore, prevention, early diagnosis, and therapeutic alternatives have been essential to avoid the future collapse of health public systems. Annexin A1 (ANXA1), a Ca2 + -dependent protein, is a promising therapeutic candidate for neurological disorders. ANXA1, found in neurons and glia, displays roles in physiological and pathological processes. Despite ANXA1 undoubtedly maintains the blood-brain barrier (BBB) integrity, this review will focus on ANXA 1 roles in neurons and glial cells. In neurons, the cytoplasmic expression of ANXA1 is associated with apoptosis, while its nuclear translocation is linked to ischemic neuronal death. Interactions with S100A11, the Tat-NTS peptide, and other molecules, modulate this translocation, suggesting potential therapeutic interventions. ANXA1 expressed on microglia modulates inflammation and efferocytosis. Post-translational modifications, such as SUMOylation, guide the role of ANXA1 in microglia polarization and neuroprotection. In addition, ANXA1 in astrocytes responds to inflammatory stimuli by influencing cytokine release. A comprehensive understanding of the intricate mechanisms of ANXA 1 in neurons and glial cells reveals promising therapeutic strategies to alleviate neuronal damage in neurological diseases. (c) 2025 Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies. (AU)

• FAPESP's process: 22/11779-8 - Toxic mechanisms of tobacco products under neutrophil production and mobilized in normal conditions and in rheumatoid arthritis
• Grantee: Pâmela Pacassa Borges
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 22/12027-0 - ANNEXIN A1 PROTEIN IN DIABETIC RETINOPATHY INFLAMMATION
• Grantee: Rafael André da Silva
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 21/00270-4 - Role of the protein Annexin A1 in the experimental model of Parkinsons Disease
• Grantee: Luiz Philipe de Souza Ferreira
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 22/02327-6 - Impact of pharmacological treatment with Annexin A1 mimetic peptide in experimental model of Parkinson's Disease
• Grantee: Cristiane Damas Gil
• Support Opportunities: Regular Research Grants
• FAPESP's process: 22/14025-4 - Effects of heated tobacco vapor, nicotine, and cigarette smoke exposures on C. elegans neuroimmune interactions and host defense
• Grantee: Pablo Rhansan dos Santos Scharf
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate