2. Academic Validation
  3. An Insight into Neuronal Processing of Ghrelin: Effects of a Bioactive Ghrelin Derivative on Proteolytic Pathways and Mitophagy

An Insight into Neuronal Processing of Ghrelin: Effects of a Bioactive Ghrelin Derivative on Proteolytic Pathways and Mitophagy

  • Mol Neurobiol. 2025 Apr 26. doi: 10.1007/s12035-025-04976-5.
Daniela Lufrano 1 2,  Chunmei Gong 3 4,  Valentina Cecarini 3,  Massimiliano Cuccioloni 3,  Laura Bonfili 3,  Chiara Sturaro 5,  Barbara Bettegazzi 6,  Chiara Ruzza 5,  Mario Perelló 7,  Mauro Angeletti 3,  Anna Maria Eleuteri 8
Affiliations

Affiliations

  • 1 School of Biosciences and Veterinary Medicine, University of Camerino, 62032, Camerino, Italy. dlufrano@biol.unlp.edu.ar.
  • 2 Departamento de Ciencias Biológicas, Facultad de Ciencias Exactas, Universidad Nacional La Plata (UNLP), CONICET, B1900 AVW, La Plata, Argentina. dlufrano@biol.unlp.edu.ar.
  • 3 School of Biosciences and Veterinary Medicine, University of Camerino, 62032, Camerino, Italy.
  • 4 Key Laboratory of Tropical Translational Medicine of the Ministry of Education, Hainan Medical University, 571199, Haikou, China.
  • 5 Department of Neuroscience and Rehabilitation, University of Ferrara, 44121, Ferrara, Italy.
  • 6 University Vita-Salute San Raffaele, 20132, Milan, Italy.
  • 7 Grupo de Neurofisiología, Instituto Multidisciplinario de Biología Celular (IMBICE), Universidad Nacional La Plata (UNLP), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET) y Comisión de Investigaciones Científicas de La Provincia de Buenos Aires (CIC-PBA), B1906 APM, La Plata, Argentina.
  • 8 School of Biosciences and Veterinary Medicine, University of Camerino, 62032, Camerino, Italy. annamaria.eleuteri@unicam.it.
PMID: 40285938 DOI: 10.1007/s12035-025-04976-5
Abstract

Protein homeostasis (proteostasis) is preserved by an orchestrated network of molecular mechanisms that regulate protein synthesis, folding, and degradation, ensuring cellular integrity and function. Proteostasis declines with age and is related to pathologies such as neurodegenerative diseases and cardiac disorders, which are accompanied by the accumulation of toxic protein aggregates. In this context, therapeutic strategies enhancing the two primary degradative systems involved in the cellular clearance of those abnormal proteins, namely ubiquitin-proteasome system and autophagy-lysosomal pathway, represent a promising approach to counteract the collapse of proteostasis in such pathological conditions. In this work, we explored the processing of ghrelin, a pleiotropic peptide hormone linked to energy metabolism and higher brain functions, which is reported to modulate the protein degradative mechanisms. According to our data, ghrelin is processed by serine hydrolases secreted into the conditioned medium of SH-SY5Y neuroblastoma cell line, commonly used in neurotoxicology and neuroscience research. Ghrelin processing leads to the formation of a shorter peptide (ghrelin(1-11)) that stimulates both the cell Proteasome system and autophagy-lysosomal pathway, encompassing the selective Autophagy of mitochondria. Our findings suggest that ghrelin processing may contribute to the maintenance of neuronal proteostasis.

Keywords

Autophagy; Ghrelin; Mitophagy; Neuronal Processing; Proteasome.

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