The Role of Calcium in Alpha-Synuclein Aggregation: A Potential Mechanism of Neurodegeneration
View/ Open
Author(s)
Primary Supervisor
Pountney, Dean
Other Supervisors
Tiralongo, Joe
Year published
2014
Metadata
Show full item recordAbstract
Abnormal protein aggregation has been implicated in the pathogenesis of many neurological disorders. This study focuses on the protein alpha-synuclein ([alpha]-syn), a pre-synaptic protein that is involved in a number of diseases collectively termed alpha-synucleinopathies, which include Parkinson's disease (PD) and Multiple System Atrophy (MSA). [alpha]-syn aggregation and microscopically-visible [alpha]-syn-positive intracellular inclusion bodies are common features of these diseases, occurring in multiple cell types and localisation throughout the central nervous system. Although gene mutations in a variety of molecular ...
View more >Abnormal protein aggregation has been implicated in the pathogenesis of many neurological disorders. This study focuses on the protein alpha-synuclein ([alpha]-syn), a pre-synaptic protein that is involved in a number of diseases collectively termed alpha-synucleinopathies, which include Parkinson's disease (PD) and Multiple System Atrophy (MSA). [alpha]-syn aggregation and microscopically-visible [alpha]-syn-positive intracellular inclusion bodies are common features of these diseases, occurring in multiple cell types and localisation throughout the central nervous system. Although gene mutations in a variety of molecular pathways have been identified in rare familial forms, the majority of [alpha]-synucleinopathy cases are sporadic in origin and have a late onset (>60 years) and therefore it is important to study age related changes in neurochemistry and how these changes may be responsible for the neurodegeneration associated with [alpha]-syn aggregation. With aging, tightly regulated cellular processes start to lose the capacity to maintain homeostasis. It is known that there is increased level of oxidative stress in aged compared to young brains, and that intracellular free calcium (Ca2+) is increased at both the resting level and upon neuronal activation. This research is focused on these two processes: firstly the increase of intracellular free Ca2+; and secondly, the increase in oxidative stress.
View less >
View more >Abnormal protein aggregation has been implicated in the pathogenesis of many neurological disorders. This study focuses on the protein alpha-synuclein ([alpha]-syn), a pre-synaptic protein that is involved in a number of diseases collectively termed alpha-synucleinopathies, which include Parkinson's disease (PD) and Multiple System Atrophy (MSA). [alpha]-syn aggregation and microscopically-visible [alpha]-syn-positive intracellular inclusion bodies are common features of these diseases, occurring in multiple cell types and localisation throughout the central nervous system. Although gene mutations in a variety of molecular pathways have been identified in rare familial forms, the majority of [alpha]-synucleinopathy cases are sporadic in origin and have a late onset (>60 years) and therefore it is important to study age related changes in neurochemistry and how these changes may be responsible for the neurodegeneration associated with [alpha]-syn aggregation. With aging, tightly regulated cellular processes start to lose the capacity to maintain homeostasis. It is known that there is increased level of oxidative stress in aged compared to young brains, and that intracellular free calcium (Ca2+) is increased at both the resting level and upon neuronal activation. This research is focused on these two processes: firstly the increase of intracellular free Ca2+; and secondly, the increase in oxidative stress.
View less >
Thesis Type
Thesis (PhD Doctorate)
Degree Program
Doctor of Philosophy (PhD)
School
School of Medical Science
Copyright Statement
The author owns the copyright in this thesis, unless stated otherwise.
Item Access Status
Public
Subject
Alpha-synucleinopathies
Parkinson’s disease (PD)
Multiple System Atrophy (MSA)
Protein alpha-synuclein