Drosophila tubulin polymerization promoting protein mutants reveal pathological correlates relevant to human Parkinson’s disease

Abstract Parkinson’s disease (PD) is a progressive neurodegenerative disorder with no known cure. PD is characterized by locomotion deficits, nigrostriatal dopaminergic neuronal loss, mitochondrial dysfunctions and formation of α-Synuclein aggregates. A well-conserved and less understood family of T...

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Autores principales:	Jing Xie, Shuting Chen, Jean C. Bopassa, Swati Banerjee
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/28fc479e7f7f4186972589d55fc1408f
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spelling	oai:doaj.org-article:28fc479e7f7f4186972589d55fc1408f2021-12-02T16:31:42ZDrosophila tubulin polymerization promoting protein mutants reveal pathological correlates relevant to human Parkinson’s disease10.1038/s41598-021-92738-32045-2322https://doaj.org/article/28fc479e7f7f4186972589d55fc1408f2021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-92738-3https://doaj.org/toc/2045-2322Abstract Parkinson’s disease (PD) is a progressive neurodegenerative disorder with no known cure. PD is characterized by locomotion deficits, nigrostriatal dopaminergic neuronal loss, mitochondrial dysfunctions and formation of α-Synuclein aggregates. A well-conserved and less understood family of Tubulin Polymerization Promoting Proteins (TPPP) is also implicated in PD and related disorders, where TPPP exists in pathological aggregates in neurons in patient brains. However, there are no in vivo studies on mammalian TPPP to understand the genetics and neuropathology linking TPPP aggregation or neurotoxicity to PD. Recently, we discovered the only Drosophila homolog of human TPPP named Ringmaker (Ringer). Here, we report that adult ringer mutants display progressive locomotor disabilities, reduced lifespan and neurodegeneration. Importantly, our findings reveal that Ringer is associated with mitochondria and ringer mutants have mitochondrial structural damage and dysfunctions. Adult ringer mutants also display progressive loss of dopaminergic neurons. Together, these phenotypes of ringer mutants recapitulate some of the salient features of human PD patients, thus allowing us to utilize ringer mutants as a fly model relevant to PD, and further explore its genetic and molecular underpinnings to gain insights into the role of human TPPP in PD.Jing XieShuting ChenJean C. BopassaSwati BanerjeeNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jing Xie Shuting Chen Jean C. Bopassa Swati Banerjee Drosophila tubulin polymerization promoting protein mutants reveal pathological correlates relevant to human Parkinson’s disease
description	Abstract Parkinson’s disease (PD) is a progressive neurodegenerative disorder with no known cure. PD is characterized by locomotion deficits, nigrostriatal dopaminergic neuronal loss, mitochondrial dysfunctions and formation of α-Synuclein aggregates. A well-conserved and less understood family of Tubulin Polymerization Promoting Proteins (TPPP) is also implicated in PD and related disorders, where TPPP exists in pathological aggregates in neurons in patient brains. However, there are no in vivo studies on mammalian TPPP to understand the genetics and neuropathology linking TPPP aggregation or neurotoxicity to PD. Recently, we discovered the only Drosophila homolog of human TPPP named Ringmaker (Ringer). Here, we report that adult ringer mutants display progressive locomotor disabilities, reduced lifespan and neurodegeneration. Importantly, our findings reveal that Ringer is associated with mitochondria and ringer mutants have mitochondrial structural damage and dysfunctions. Adult ringer mutants also display progressive loss of dopaminergic neurons. Together, these phenotypes of ringer mutants recapitulate some of the salient features of human PD patients, thus allowing us to utilize ringer mutants as a fly model relevant to PD, and further explore its genetic and molecular underpinnings to gain insights into the role of human TPPP in PD.
format	article
author	Jing Xie Shuting Chen Jean C. Bopassa Swati Banerjee
author_facet	Jing Xie Shuting Chen Jean C. Bopassa Swati Banerjee
author_sort	Jing Xie
title	Drosophila tubulin polymerization promoting protein mutants reveal pathological correlates relevant to human Parkinson’s disease
title_short	Drosophila tubulin polymerization promoting protein mutants reveal pathological correlates relevant to human Parkinson’s disease
title_full	Drosophila tubulin polymerization promoting protein mutants reveal pathological correlates relevant to human Parkinson’s disease
title_fullStr	Drosophila tubulin polymerization promoting protein mutants reveal pathological correlates relevant to human Parkinson’s disease
title_full_unstemmed	Drosophila tubulin polymerization promoting protein mutants reveal pathological correlates relevant to human Parkinson’s disease
title_sort	drosophila tubulin polymerization promoting protein mutants reveal pathological correlates relevant to human parkinson’s disease
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/28fc479e7f7f4186972589d55fc1408f
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Drosophila tubulin polymerization promoting protein mutants reveal pathological correlates relevant to human Parkinson’s disease

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