Neurodegeneration with Brain Iron Accumulation (NBIA) refers to a group of hereditary neurodegenerative disorders characterized by iron accumulation in basal ganglia, including the globus pallidus and substantia nigra. Among the various subtypes, mitochondrial membrane protein-associated neurodegeneration (MPAN), which represents approximately 30% of NBIA cases, results from mutations in the last exon of the C19orf12 gene and is characterized by spastic paraplegia, parkinsonism and psychiatric symptoms. This project aims to characterize a Drosophila melanogaster model of MPAN based on the silencing of two C19orf12 fly orthologs, CG3740 and CG11617. More specifically, the expression of the genes of interest was reduced in different tissues and neuronal populations through RNA interference. I then assessed MPAN-related phenotypes in single and double-knockdown flies and investigated whether the observed phenotypes could be connected with neuronal autophagic alterations. The collected results indicate that reduced levels of the CG3740 and CG11671 proteins affect locomotion in both larvae and adult flies and promote eye defects supporting the validity of our fly lines as an experimental model to study MPAN. In contrast, our data do not support the involvement of autophagy in the disease pathology.
Neurodegeneration with Brain Iron Accumulation (NBIA) refers to a group of hereditary neurodegenerative disorders characterized by iron accumulation in basal ganglia, including the globus pallidus and substantia nigra. Among the various subtypes, mitochondrial membrane protein-associated neurodegeneration (MPAN), which represents approximately 30% of NBIA cases, results from mutations in the last exon of the C19orf12 gene and is characterized by spastic paraplegia, parkinsonism and psychiatric symptoms. This project aims to characterize a Drosophila melanogaster model of MPAN based on the silencing of two C19orf12 fly orthologs, CG3740 and CG11617. More specifically, the expression of the genes of interest was reduced in different tissues and neuronal populations through RNA interference. I then assessed MPAN-related phenotypes in single and double-knockdown flies and investigated whether the observed phenotypes could be connected with neuronal autophagic alterations. The collected results indicate that reduced levels of the CG3740 and CG11671 proteins affect locomotion in both larvae and adult flies and promote eye defects supporting the validity of our fly lines as an experimental model to study MPAN. In contrast, our data do not support the involvement of autophagy in the disease pathology.
Generation and characterization of a Drosophila melanogaster model of Neurodegeneration with Brain Iron Accumulation.
GUIDORIZZI, SOFIA
2024/2025
Abstract
Neurodegeneration with Brain Iron Accumulation (NBIA) refers to a group of hereditary neurodegenerative disorders characterized by iron accumulation in basal ganglia, including the globus pallidus and substantia nigra. Among the various subtypes, mitochondrial membrane protein-associated neurodegeneration (MPAN), which represents approximately 30% of NBIA cases, results from mutations in the last exon of the C19orf12 gene and is characterized by spastic paraplegia, parkinsonism and psychiatric symptoms. This project aims to characterize a Drosophila melanogaster model of MPAN based on the silencing of two C19orf12 fly orthologs, CG3740 and CG11617. More specifically, the expression of the genes of interest was reduced in different tissues and neuronal populations through RNA interference. I then assessed MPAN-related phenotypes in single and double-knockdown flies and investigated whether the observed phenotypes could be connected with neuronal autophagic alterations. The collected results indicate that reduced levels of the CG3740 and CG11671 proteins affect locomotion in both larvae and adult flies and promote eye defects supporting the validity of our fly lines as an experimental model to study MPAN. In contrast, our data do not support the involvement of autophagy in the disease pathology.File | Dimensione | Formato | |
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https://hdl.handle.net/20.500.12608/84214