The protein alpha-synuclein (a-syn) is by far the most vetted pathogenic participant in the neurodegeneration that occurs in Parkinson’s disease (PD) and other synucleinopathies such as multiple system atrophy (MSA). Although the precise role of this protein in disease pathogenesis is unknown, its toxicity is largely considered to be due the formation of toxic intracellular aggregates. As such, targeting a-syn directly is being heavily investigated as a potential therapeutic avenue in PD. Nevertheless, the precise normal function(s) of this protein in neurons of the central and autonomic nervous systems (and other cells) is largely unknown, and a multitude of work has shown that removing this protein from neurons also has a profound effect on a variety of intracellular processes, and in some cases leads to neurodegeneration. Such findings have led some to postulate that a-syn has certain functions that are crucial to some populations of neurons, and that perhaps its role in disease can be explained as a toxic loss of function as a result of its sequestration into aggregates. Regardless of the precise role of a-syn in disease, it is crucial that the role of this protein in normal neuronal function is thoroughly defined as the field moves forward with a-syn modulating therapies. Indeed, a-syn is one of the most abundant proteins of the nervous system, and can be found both centrally and in the peripheral nervous system. Although this protein is most often associated with a role in neurotransmission, a plethora of work has attributed a role of a-syn to disparate functions such as mitochondrial function, neurotransmitter production, and calcium homeostasis, amongst others.
This research topic aims to elicit articles which look at a-syn function, both in the context of a healthy neuron, functional changes of this protein with aging, and in disease. Some important questions to be considered are: 1) Are there functions, that when disrupted, can lead to neuronal loss? 2) Is a disruption in these functions responsible for the autonomic dysfunction that is observed in a majority of patients? 3) Are there functional roles of this protein that can lead to toxicity associated with changes in its localization or with aging? 4) Are there other factors (in the disease state) that can alter a-syn function? 5) Do changes in expression or disease mutations lead to altered homeostasis and function? Accordingly, this research topic is expected to cover an extensive range of various topics aimed at improving our understanding as to the role of this seemingly important protein.
The protein alpha-synuclein (a-syn) is by far the most vetted pathogenic participant in the neurodegeneration that occurs in Parkinson’s disease (PD) and other synucleinopathies such as multiple system atrophy (MSA). Although the precise role of this protein in disease pathogenesis is unknown, its toxicity is largely considered to be due the formation of toxic intracellular aggregates. As such, targeting a-syn directly is being heavily investigated as a potential therapeutic avenue in PD. Nevertheless, the precise normal function(s) of this protein in neurons of the central and autonomic nervous systems (and other cells) is largely unknown, and a multitude of work has shown that removing this protein from neurons also has a profound effect on a variety of intracellular processes, and in some cases leads to neurodegeneration. Such findings have led some to postulate that a-syn has certain functions that are crucial to some populations of neurons, and that perhaps its role in disease can be explained as a toxic loss of function as a result of its sequestration into aggregates. Regardless of the precise role of a-syn in disease, it is crucial that the role of this protein in normal neuronal function is thoroughly defined as the field moves forward with a-syn modulating therapies. Indeed, a-syn is one of the most abundant proteins of the nervous system, and can be found both centrally and in the peripheral nervous system. Although this protein is most often associated with a role in neurotransmission, a plethora of work has attributed a role of a-syn to disparate functions such as mitochondrial function, neurotransmitter production, and calcium homeostasis, amongst others.
This research topic aims to elicit articles which look at a-syn function, both in the context of a healthy neuron, functional changes of this protein with aging, and in disease. Some important questions to be considered are: 1) Are there functions, that when disrupted, can lead to neuronal loss? 2) Is a disruption in these functions responsible for the autonomic dysfunction that is observed in a majority of patients? 3) Are there functional roles of this protein that can lead to toxicity associated with changes in its localization or with aging? 4) Are there other factors (in the disease state) that can alter a-syn function? 5) Do changes in expression or disease mutations lead to altered homeostasis and function? Accordingly, this research topic is expected to cover an extensive range of various topics aimed at improving our understanding as to the role of this seemingly important protein.
