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Updated: May 8, 2026

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Análisis de epimutaciones revela la participación de la vía de señalización SLIT2/ROBO en la neuropatía diabética

Katarzyna Malgorzata Kwiatkowska¹, Paolo Garagnani^2,3, Francesca Ferraresi⁴

¹Department of Medical and Surgical Sciences (DIMEC), University of Bologna, 40126, Bologna, Italy. katarzyn.kwiatkowsk2@unibo.it.

|January 10, 2026

Abstract:

Changes in gene function or expression caused by epigenetic modifications may play a role in painful diabetic neuropathy. Two independent cohorts of patients deeply phenotyped for painful diabetic neuropathy underwent whole genome DNA methylation data analysis. Burden of rare site events at the global, chromosomal and gene level; epigenetic homogeneity for regions enriched in epivariants (epilesions) and functional analysis of the genes with stochastic phenomena was undertaken. This revealed significant involvement of the SLIT/ROBO signaling axis-engaged in peripheral nerve regeneration after injury, among several molecular pathways, making it an attractive therapeutic target in patients with diabetic painful neuropathy.

Palabras clave:

Envejecimiento biológico Metilación del ADN Neuropatía diabética Deriva epigenética Epivariantes Dolor neuropático Mutaciones epigenéticas estocásticas

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Diabetic Neuropathy

Diabetic Neuropathy

DefinitionDiabetic neuropathy is nerve damage caused by long-standing diabetes mellitus. It results directly from prolonged high blood sugar levels.PathophysiologyThe pathophysiology of diabetic neuropathy involves both metabolic and vascular disturbances triggered by chronic hyperglycemia.Metabolic injury: Elevated glucose levels activate the polyol pathway within nerve cells, leading to the accumulation of sorbitol and fructose. This increases oxidative stress, disrupts normal nerve...