A Role for Small Ubiquitin-like Modifier (SUMO-1) in the Autophagic Response to Protein Aggregates in Neurodegeneration
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Author(s)
Pountney, Dean Louis
Griffith University Author(s)
Year published
2012
Metadata
Show full item recordAbstract
Many neurodegenerative diseases are characterised by
microscopically-visible protein aggregates, or inclusion bodies, within
neural cells. Initially found in intranuclear inclusions in hereditary ataxias
and Huntington’s disease, the ubiquitin homologue, SUMO-1, has now
been shown in a range of neurodegenerative diseases in both nuclear
and cytoplasmic inclusions, and marks sub-domains in Lewy bodies
and in glial cytoplasmic α-synuclein inclusions. Proteomic analysis of
intranuclear inclusion bodies revealed that SUMO-1 was associated
with proteins of the endomembrane system. In recent studies, we
have found that SUMO-1 is ...
View more >Many neurodegenerative diseases are characterised by microscopically-visible protein aggregates, or inclusion bodies, within neural cells. Initially found in intranuclear inclusions in hereditary ataxias and Huntington’s disease, the ubiquitin homologue, SUMO-1, has now been shown in a range of neurodegenerative diseases in both nuclear and cytoplasmic inclusions, and marks sub-domains in Lewy bodies and in glial cytoplasmic α-synuclein inclusions. Proteomic analysis of intranuclear inclusion bodies revealed that SUMO-1 was associated with proteins of the endomembrane system. In recent studies, we have found that SUMO-1 is associated with lysosomes both in neurodegenerative diseases and in rodent and cellular disease models. We examined brain tissue from cases of progressive supranuclear palsy (PSP), multiple system atrophy (MSA) and normal controls and identified co-localisation of the lysosomal marker, cathepsin D, and SUMO-1 associated with both the tau-positive PSP inclusions and the α-synuclein-positive MSA inclusions. Rat and mouse models of Parkinson’s disease were investigated that employ unilateral injection of the mitochondrial complex 1 inhibitor, rotenone and revealed the association of SUMO-1 with lysosomes and α-synuclein intracellular inclusion bodies in the lesioned brain tissue. The OLN oligodendrocyte cell model recapitulates PSP-like tau inclusions and showed associated SUMO-1-positive lysosomes. SUMO-1-positive lysosomes were also associated both with polyglutamine aggregates in Httexon1-Q74-eGFP transfected cells and with α-synuclein aggregates in α-synuclein overexpressing cells. Western analysis of purified lysosomes revealed an increase of SUMO-1 in the lysosomal fraction. These findings suggest a role for SUMO-1 in the autophagy pathway in neurodegeneration.
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View more >Many neurodegenerative diseases are characterised by microscopically-visible protein aggregates, or inclusion bodies, within neural cells. Initially found in intranuclear inclusions in hereditary ataxias and Huntington’s disease, the ubiquitin homologue, SUMO-1, has now been shown in a range of neurodegenerative diseases in both nuclear and cytoplasmic inclusions, and marks sub-domains in Lewy bodies and in glial cytoplasmic α-synuclein inclusions. Proteomic analysis of intranuclear inclusion bodies revealed that SUMO-1 was associated with proteins of the endomembrane system. In recent studies, we have found that SUMO-1 is associated with lysosomes both in neurodegenerative diseases and in rodent and cellular disease models. We examined brain tissue from cases of progressive supranuclear palsy (PSP), multiple system atrophy (MSA) and normal controls and identified co-localisation of the lysosomal marker, cathepsin D, and SUMO-1 associated with both the tau-positive PSP inclusions and the α-synuclein-positive MSA inclusions. Rat and mouse models of Parkinson’s disease were investigated that employ unilateral injection of the mitochondrial complex 1 inhibitor, rotenone and revealed the association of SUMO-1 with lysosomes and α-synuclein intracellular inclusion bodies in the lesioned brain tissue. The OLN oligodendrocyte cell model recapitulates PSP-like tau inclusions and showed associated SUMO-1-positive lysosomes. SUMO-1-positive lysosomes were also associated both with polyglutamine aggregates in Httexon1-Q74-eGFP transfected cells and with α-synuclein aggregates in α-synuclein overexpressing cells. Western analysis of purified lysosomes revealed an increase of SUMO-1 in the lysosomal fraction. These findings suggest a role for SUMO-1 in the autophagy pathway in neurodegeneration.
View less >
Conference Title
Australian Neuroscience Society Annual Meeting 2012
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Copyright Statement
© The Author(s) 2012. The attached file is reproduced here in accordance with the copyright policy of the publisher. For information about this conference please refer to the conference’s website or contact the author.
Subject
Neurology and Neuromuscular Diseases