About this Research Topic
Dopaminergic nigro-striatal neuronal loss in Parkinson’s Disease (PD) is a slow, uncontrollable process. Since little is known about the underlying mechanisms of PD, current PD therapy can only counteract symptoms.
The main focus of this Research Topic is to describe some of the key unresolved pathophysiological questions in PD through a pre-clinical and clinical approach. The Research Topic will focus on the most important risk factors involved in dopamine neuron degeneration: α-synuclein, neuroinflammation, and mitochondrial dysfunction. Plastic changes taking place during development of dopamine neurodegeneration will also be described.
These aspects will be presented by multiple authors. Specifically:
• The role of α-synuclein will be described by identifying the factors that modulate α-synuclein accumulation and aggregation. The different contributions will describe how monoubiquitination leads to the proteasomal degradation of α-synuclein and how SUMOylation of α-synuclein leads to its accumulation. Animal models of alpha-synuclein aggregates-mediated neurodegeneration will be presented. Moreover, results on PIAS2 expression along with SUMOylated α-synuclein increase in PD brains will be presented, together with novel targets for treating the disease and drugs that inhibit α-synuclein neurotoxic effects.
• The role played by mitochondrial dysfunctions in models of neurodegeneration or neuroinflammation will be also presented. These studies will include results on changes in mitochondrial morphology in A-kinase anchor protein (AKP1) and Na/K exchanger (NCX3).
• The role of neuroinflammation in neurodegeneration will be described in relation to glia activation, cytokine, and interleukin production in genetic or drug-induced models of progressive dopamine neuron degeneration. The effects of new drugs on markers of neuroinflammation will be also presented.
• The role of glucocerebrosidase defects and urate concentrations in the progression of PD will be defined, as these two factors have been correlated to increase risk of developing PD.
• The role of plasticity of the nigro-striatal system in response to dopamine neuron degeneration and to neuroinflammation will be also presented.
In addition, specific studies will describe changes in olfaction and taste sensitivity and in microbioma composition as well as the role played by hyperglycemia in the evolution of PD.
Keywords: Parkinson's Disease, α-synuclein, neuroinflammation, mitochondrial dysfunction
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