OPA1 Deficiency Impairs NGF Signaling and Drives Sympathetic Neurodegeneration

Marco Ronfini; Valentina Prando; Vittoria Di Mauro; Lolita Dokshokova; Erika Lazzeri; Irene Costantini; Lukas Alàn; Erwan Andre Riviere; Alex Incensi; Camilla Olianti; Chiara La Morgia; Rocco Liguori; Leonardo Sacconi; Vincenzo Donadio; Luca Scorrano; Valerio Carelli; Marco Mongillo; Tania Zaglia

doi:10.1016/j.jacbts.2025.101460

OPA1 Deficiency Impairs NGF Signaling and Drives Sympathetic Neurodegeneration

JACC Basic Transl Sci. 2026 Feb;11(2):101460. doi: 10.1016/j.jacbts.2025.101460.

Authors

Marco Ronfini¹, Valentina Prando¹, Vittoria Di Mauro¹, Lolita Dokshokova¹, Erika Lazzeri², Irene Costantini³, Lukas Alàn⁴, Erwan Andre Riviere⁴, Alex Incensi⁵, Camilla Olianti², Chiara La Morgia⁶, Rocco Liguori⁶, Leonardo Sacconi⁷, Vincenzo Donadio⁶, Luca Scorrano⁴, Valerio Carelli⁶, Marco Mongillo⁸, Tania Zaglia⁹

Affiliations

¹ Department of Biomedical Sciences, University of Padova, Padova, Italy; Veneto Institute of Molecular Medicine, Padova, Italy.
² European Laboratory for Non-linear Spectroscopy, University of Florence, Florence, Italy.
³ European Laboratory for Non-linear Spectroscopy, University of Florence, Florence, Italy; National Institute of Optics, National Research Council, University of Florence, Florence, Italy; Department of Biology, University of Florence, Italy.
⁴ Veneto Institute of Molecular Medicine, Padova, Italy; Department of Biology, University of Padova, Italy.
⁵ IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy.
⁶ IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy; Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy.
⁷ Institute of Clinical Physiology, National Research Council, Florence, Italy; Institute for Experimental Cardiovascular Medicine, University Heart Center and Medical Faculty, University of Freiburg, Freiburg, Germany.
⁸ Department of Biomedical Sciences, University of Padova, Padova, Italy; Veneto Institute of Molecular Medicine, Padova, Italy; CNR Institute of Neuroscience, Padova, Italy; Interdepartmental Research Center of Myology (cirMYO), Padova, Italy.
⁹ Department of Biomedical Sciences, University of Padova, Padova, Italy; Veneto Institute of Molecular Medicine, Padova, Italy; Interdepartmental Research Center of Myology (cirMYO), Padova, Italy. Electronic address: tania.zaglia@unipd.it.

Abstract

Peripheral sympathetic neurodegeneration drives cardiac dysfunction in dominant optic atrophy, revealing a critical neuro-cardiac link. Optic atrophy factor-1 haploinsufficiency disrupts mitochondrial dynamics and neurotrophic signaling, causing targeted sympathetic denervation and arrhythmias. Restoring nerve growth factor transport and mitochondrial health in sympathetic neurons represents a promising therapeutic avenue for cardiac autonomic disorders. Future research must unravel mechanisms of neurocardiac crosstalk to develop precise interventions against neurogenic cardiac disease progression.

Keywords: dominant optic atrophy; mitochondria; nerve growth factor; optic atrophy factor-1; sympathetic neurons.