TY - JOUR
T1 - Impacts of hnRNP A1 Splicing Inhibition on the Brain Remyelination Proteome
AU - Brandão-Teles, Caroline
AU - Carregari, Victor Corasolla
AU - Reis-de-Oliveira, Guilherme
AU - Smith, Bradley J.
AU - Chaves, Yane
AU - Sousa Santos, Aline Valéria
AU - Pinheiro, Erick Martins de Carvalho
AU - Oliveira, Caio C.
AU - Vieira, Andre Schwambach
AU - Crunfli, Fernanda
AU - Martins-de-Souza, Daniel
N1 - Publisher Copyright:
© 2025 The Author(s). Journal of Neurochemistry published by John Wiley & Sons Ltd on behalf of International Society for Neurochemistry.
PY - 2025/1
Y1 - 2025/1
N2 - 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. (Figure presented.)
AB - 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. (Figure presented.)
UR - http://www.scopus.com/inward/record.url?scp=85215824561&partnerID=8YFLogxK
U2 - 10.1111/jnc.16304
DO - 10.1111/jnc.16304
M3 - Journal article
C2 - 39840781
AN - SCOPUS:85215824561
SN - 0022-3042
VL - 169
JO - Journal of Neurochemistry
JF - Journal of Neurochemistry
IS - 1
M1 - e16304
ER -