Impacts of hnRNP A1 Splicing Inhibition on the Brain Remyelination Proteome

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Brandao-Teles, Caroline ; Carregari, Victor Corasolla ; Reis-de-Oliveira, Guilherme ; Smith, Bradley J. ; Chaves, Yane ; Sousa Santos, Aline Valeria ; Pinheiro, Erick Martins de Carvalho ; Oliveira, Caio C. ; Vieira, Andre Schwambach ; Crunfli, Fernanda ; Martins-de-Souza, Daniel

• Document type: Journal article
• Source: Journal of Neurochemistry; v. 169, n. 1, p. 16-pg., 2025-01-01.

Abstract

Oligodendrocytes, the myelinating cells in the central nervous system, are implicated in several neurological disorders marked by dysfunctional RNA-binding proteins (RBPs). The present study aimed at investigating the role of hnRNP A1 in the proteome of the corpus callosum, prefrontal cortex, and hippocampus of a murine cuprizone-induced demyelination model. Right after the cuprizone insult, we administered an hnRNP A1 splicing activity inhibitor and analyzed its impact on brain remyelination by nanoESI-LC-MS/MS label-free proteomic analysis to assess the biological processes affected in these brain regions. Significant alterations in essential myelination proteins highlighted the involvement of hnRNP A1 in maintaining myelin integrity. Pathways related to sphingolipid and endocannabinoid signaling were affected, as well as the synaptic vesicle cycle and GABAergic synapses. Although behavioral impairments were not observed, molecular changes suggest potential links to memory, synaptic function, and neurotransmission processes. These findings enhance our understanding of the multifaceted roles of hnRNP A1 in the central nervous system, providing valuable insights for future investigations and therapeutic interventions in neurodegenerative and demyelinating diseases.image (AU)

• FAPESP's process: 19/22398-2 - The role of cholesterol synthesis in the mode of action of clozapine in schizophrenia models
• Grantee: Fernanda Crunfli
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 17/25588-1 - From the basic understanding to clinical biomarkers to schizophrenia: a neuroproteomics-centered multidisciplinary study
• Grantee: Daniel Martins-de-Souza
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 18/01669-5 - New quiral metal catalysts and their applications in asymmetric catalysis
• Grantee: Caio Costa Oliveira
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 23/08885-3 - Cellular and Functional Characterization of Schizophrenia iPSC-derived Microglia
• Grantee: Aline Valéria Sousa Santos
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 18/01410-1 - Evaluating the effects of clozapine on immune system cells
• Grantee: Guilherme Reis-De-Oliveira
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 19/05155-9 - The role of the glycoproteome and phosphoproteome during neuronal differentiation in schizophrenia
• Grantee: Victor Corasolla Carregari
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 23/11514-7 - Synthesis of Ru(II)-oxazoline complexes and application in C-H functionalization.
• Grantee: Erick Martins de Carvalho Pinheiro
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)